Abdel Tahari

Head and Neck PET/CT: Therapy Response Interpretation Criteria (Hopkins Criteria)—Interreader Reliability, Accuracy, and Survival Outcomes

There has been no established qualitative system of interpretation for therapy response assessment using PET/CT for head and neck cancers. The objective of this study was to validate the Hopkins interpretation system to assess therapy response and survival outcome in head and neck squamous cell cancer patients (HNSCC). Methods: The study included 214 biopsy-proven HNSCC patients who underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3 nuclear medicine physicians, independently. The studies were scored using a qualitative 5-point scale, for the primary tumor, for the right and left neck, and for overall assessment. Scores 1, 2, and 3 were considered negative for tumors, and scores 4 and 5 were considered positive for tumors. The Cohen κ coefficient (κ) was calculated to measure interreader agreement. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan–Meier plots with a Mantel–Cox log-rank test and Gehan Breslow Wilcoxon test for comparisons. Results: Of the 214 patients, 175 were men and 39 were women. There was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall, left neck, right neck, and primary tumor site response scores, respectively. The corresponding κ coefficients for interreader agreement between readers were, 0.69–0.79, 0.68–0.83, 0.69–0.87, and 0.79–0.86 for overall, left neck, right neck, and primary tumor site response, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%, respectively. Cox multivariate regression analysis showed human papillomavirus (HPV) status and PET/CT interpretation were the only factors associated with PFS and OS. Among the HPV-positive patients (n = 123), there was a significant difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03–0.57; P = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00–0.13; P = 0.0006) between the patients who had a score negative for residual tumor versus positive for residual tumor. A similar significant difference was observed in PFS and OS for all patients. There was also a significant difference in the PFS of patients with PET-avid residual disease in one site versus multiple sites in the neck (HR, 0.23; log-rank P = 0.004). Conclusion: The Hopkins 5-point qualitative therapy response interpretation criteria for head and neck PET/CT has substantial interreader agreement and excellent negative predictive value and predicts OS and PFS in patients with HPV-positive HNSCC.

Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application

Static whole-body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting the axial field-of-view to ~15-20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition protocol of ~45 min total length is presented, composed of (i) an initial 6 min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (six passes × seven bed positions, each scanned for 45 s). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of ten different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole body. In addition, the total acquisition length can be reduced from 45 to ~35 min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error and the CNR metrics, resulting in enhanced task-based imaging.

SPECT Analysis of Cardiac Perfusion Changes After Whole- Breast/Chest Wall Radiation Therapy With or Without Active Breathing Coordinator: Results of a Randomized Phase 3 Trial

PURPOSE Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. METHODS AND MATERIALS Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before and 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segments perfusion. Scores were analyzed with nonparametric tests and linear regression. RESULTS Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. CONCLUSIONS In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.

Follow-up or Surveillance 18F-FDG PET/CT and Survival Outcome in Lung Cancer Patients

The value of performing follow-up PET/CT imaging more than 6 mo after the conclusion of therapy—either as a routine practice or because of clinically suspected recurrence—is not well established. The purpose of this study was to evaluate the added value of follow-up PET/CT to the clinical assessment and survival outcome of lung cancer patients. Methods: This was a retrospective study of 261 biopsy-proven lung cancer patients at a single tertiary center. In total, 488 follow-up PET/CT scans done 6 or more months after the completion of initial treatment were included in this study. Median follow-up from the completion of primary treatment was 29.3 mo (range, 6.1–295.1 mo). Overall survival (OS) benefit was measured using Kaplan–Meier plots with a Mantel–Cox log-rank test. A multivariate Cox regression model was provided with clinical covariates. Results: Of the 488 PET/CT scans, 281 were positive and 207 negative for recurrence. Overall median survival from the time of the PET/CT study was 48.5 mo. The median survival of PET-positive and PET-negative groups was 32.9 and 81.6 mo, respectively (P < 0.0001). A subgroup analysis demonstrated a similar difference in OS for 212 scans completed between 6 and 24 mo after treatment (P = 0.0004) and 276 scans completed after 24 mo (P = 0.0006). In the context of clinical assessment, PET/CT identified recurrence in 43.7% (107/245) of scans without prior clinical suspicion and ruled out recurrence in 15.2% (37/243) of scans with prior clinical suspicion. There was a significant difference in OS when grouped by clinical suspicion (P = 0.0112) or routine follow-up (P < 0.0001). In a multivariate Cox regression model, factors associated with OS were age (P < 0.0001) and PET/CT result (P = 0.0003). An age-stratified subgroup analysis demonstrated a significant difference in OS by PET scan result among patients younger than 60 y and between 60 and 70 y but not in those older than 70 y (P < 0.0001, P = 0.0004, and P = 0.8193, respectively). Conclusion: 18F-FDG PET/CT performed for follow-up more than 6 mo after the completion of primary treatment adds value to clinical judgment and is a prognostic marker of OS in lung cancer patients, regardless of the timing of the follow-up scan, and especially in patients younger than 70 y.

Optimum Lean Body Formulation for Correction of Standardized Uptake Value in PET Imaging

Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is becoming a popular metric for quantitative assessment of clinical PET. Sex-specific quantitative effects of different LBM formulations on liver SUV have not been well studied. Methods: 18F-FDG PET/CT scans from 1,033 consecutive adult (501 women, 532 men) studies were reviewed. Liver SUV was measured with a 3-cm-diameter spheric region of interest in the right hepatic lobe and corrected for LBM using the sex-specific James and Janmahasatian formulations. Results: Body weight was 71.0 ± 20.7 kg (range, 18.0–175.0 kg) and 82.9 ± 18.6 kg (range, 23.0–159.0 kg) for women and men, respectively. SUV, based on body weight, has a significantly positive correlation with weight for both women (r = 0.58, P < 0.0001) and men (r = 0.54, P < 0.0001). This correlation is reduced in men (r = 0.11, P = 0.01) and becomes negative for women (r = −0.35, P = 0.0001) with the James formulation of SUL. This negative correlation was eliminated when the very obese women (body mass index ≥ 35) were excluded from the analysis (r = 0.13, P = 0.8). The Janmahasatian formulation annuls the correlation between SUL and weight for women (r = 0.04, P = 0.4) and decreases it for men (r = 0.13, P = 0.003). Conclusion: Hepatic correction with the more common James formulation for body lean mass breaks down and shows low SUL values in very obese patients. The adoption of the Janmahasatian formula for estimation of LBM in modern PET scanners and display workstations is recommended, in view of the increasing frequency of obesity.

FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: Characteristics of human papillomavirus-positive and -negative tumors

Objective The objective of this study was to assess differences in morphological and glycolytic characteristics of primary tumors and locoregional nodal disease between human papillomavirus (HPV)–positive and HPV-negative oropharyngeal head and neck squamous cell carcinoma. Methods This was a retrospective analysis of 123 baseline FDG PET/CT scans from patients (aged 57.0 ± 10.6 years) with newly diagnosed oropharyngeal SCC between January 2003 and June 2012. There were 98 HPV-positive and 25 HPV-negative patients. SUVmax, SUVpeak, and SUVmean based on lean body mass, as well as RECIST (Response Evaluation Criteria In Solid Tumors) dimensions, metabolic tumor volume (gradient and threshold-segmentation methods) and total lesion glycolysis, were determined for primary and locoregional nodal disease. Results Human papillomavirus–negative primary tumors were significantly larger as measured by RECIST longest diameter (P = 0.002) and slightly more heterogeneous as measured by the heterogeneity index (P = 0.07), higher SUVmax (P < 0.01), SUVpeak (P = 0.01), SUVmean (P = 0.01), metabolic tumor volume (P = 0.002), and total lesion glycolysis (P = 0.001), for both segmentation methods. Index parameters of HPV-positive nodal disease tend to be larger, but some with no statistical significance (P > 0.05). There was no significant difference in the metabolic parameters of primary tumor or nodal metastases for HPV-positive patients with and without smoking history. Conclusions Index morphologic and glycolytic parameters as measured in FDG PET/CT are significantly larger in HPV-negative as compared with HPV-positive primary oropharyngeal carcinoma. In contrast, the same parameters trended to be larger in HPV-positive regional nodal disease.

Addition of 18F-FDG PET/CT to Clinical Assessment Predicts Overall Survival in HNSCC: A Retrospective Analysis with Follow-up for 12 Years

18F-FDG PET/CT is used in the follow-up of patients with head and neck squamous cell cancer (HNSCC). However, its impact on clinical decision making and patient outcome is not fully established. The objective of this study was to determine the prognostic value of 18F-FDG PET/CT for overall survival (OS) of HNSCC patients when performed in addition to clinical assessment between 4 and 24 mo after treatment. Methods: This was a retrospective study at a single tertiary center. The institutional review board approved this study, and the requirement to obtain informed consent was waived. The study included 134 biopsy-proven HNSCC patients with 227 follow-up PET/CT scans. The primary outcome measure was OS. Median follow-up was 40 mo (range, 7–145 mo). Survival is presented as Kaplan–Meier plots with Mantel–Cox log-rank test. The multivariate Cox model included clinical covariates. Results: Of the 227 PET/CT scans, 41 (18%) were positive for tumor and 186 (82%) were negative for tumor. PET/CT identified recurrence in 5% (9/194) of scans performed without prior clinical concern and ruled out tumor in 51.5% (17/33) of scans performed to evaluate clinical suspicion or uncertainty of recurrence. The median survival of PET-positive and -negative groups from the date of the scan was 20 and 30.5 mo, respectively (P < 0.0001). There was a significant difference in OS from the scan date between patients who had a positive PET/CT result for tumor and those who had a negative result (log-rank, P < 0.0001), with a hazard ratio of 29.74. Human papillomavirus status (P = 0.001) and PET/CT result (P = 0.04) were the only factors significantly associated with OS, adjusted for all other covariates. Conclusion: 18F-FDG PET/CT performed between 4 and 24 mo after treatment adds value to clinical assessment at the time of the study, especially when there is clinical suspicion or uncertainty, and can serve as a prognostic marker of OS in HNSCC.

Brain FDG PET and the diagnosis of dementia

OBJECTIVE We review the role of brain FDG PET in the diagnosis of Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and vascular dementia. Characteristic spatial patterns of brain metabolism on FDG PET can help differentiate various subtypes of dementia. CONCLUSION In patients with different subtypes of dementia, FDG PET/CT shows distinct spatial patterns of metabolism in the brain and can help clinicians to make a reasonably accurate and early diagnosis for appropriate management or prognosis.

Prognostic Value of FDG PET Metabolic Tumor Volume in Human Papillomavirus–Positive Stage III and IV Oropharyngeal Squamous Cell Carcinoma

OBJECTIVE The purpose of this study was to establish the prognostic utility in human papillomavirus (HPV)-positive stage III and IV oropharyngeal squamous cell carcinoma (SCC) of the (18)F-FDG parameters maximal, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). MATERIALS AND METHODS We included 70 patients in the present study who had a biopsy-proven HPV-positive (by in situ hybridization) stage III and IV oropharyngeal SCC and had a baseline PET/CT examination at our institution. Outcome endpoint was event-free survival (EFS), which included recurrence-free and overall survival. Cox proportional hazards multivariate regression analyses were performed. Survival analysis was performed using Kaplan-Meier survival curves. RESULTS In Cox regression proportional hazard univariate analysis, total MTV (hazard ratio [HR], 1.02; p = 0.008), primary-tumor MTV (HR, 1.02; p = 0.024), neck nodal MTV (HR, 1.03; p = 0.006), neck nodal TLG (HR, 1.01; p = 0.006), and neck node status (HR, 4.45; p = 0.03) showed a statistically significant association with EFS. There was no statistically significant association of EFS with SUVmax, SUVmean, SUVpeak, and primary-tumor or overall TLG. In Cox regression proportional hazard multivariate model I, total MTV remained an independent prognostic marker for EFS when adjusted for every other variable individually in the model; in model II, primary-tumor MTV, neck node status, and SUVpeak are independent prognostic markers for EFS. The Kaplan-Meier survival curves using optimum cut point of 41 mL of total MTV were not significant (p = 0.09). CONCLUSION Total MTV and primary-tumor MTV are associated with survival outcomes in patients with HPV-positive stage III and IV oropharyngeal SCC.

Cardiac PET/CT Misregistration Causes Significant Changes in Estimated Myocardial Blood Flow

Misregistration of cardiac PET/CT data can lead to misinterpretation of regional myocardial perfusion. However, the effect of misregistration on the quantification of myocardial blood flow (MBF) has not been studied. Methods: Cardiac 82Rb-PET/CT scans of 10 patients with normal regional myocardial perfusion were analyzed. Realignment was done for the baseline and stress PET/CT images as necessary, and MBF was obtained from dynamic data. Then, the stress images were misregistered by 5 mm along the x-axis (left) and z-axis (cranial) and again by 10 mm. A 10-mm misregistration in the opposite direction (−10 mm along the x-axis [right] and z-axis [caudal]) was also tested. Stress MBF was recalculated for 5-, 10-, and −10-mm misregistrations. Results: Stress MBF of the left ventricle decreased by 10% ± 6% (P = 0.005) after 5-mm misregistration and by 24% ± 15% (P = 0.001) after 10-mm misregistration. In descending order, the most important stress MBF changes occurred in the anterior (39% ± 9%), lateral (34% ± 9%), apical (20% ± 16%), inferior (12% ± 10%), and septal (10% ± 12%) walls after 10-mm misregistration. Lesser changes were observed after 5-mm misregistration, with the same wall distribution. In contrast, −10-mm misregistration increased global MBF by 9% ± 6% (P = 0.004). In descending order, the overestimation of estimated MBF after −10-mm misregistration occurred in the lateral (15% ± 8%), apical (15% ± 18%), anterior (9% ± 5%), and inferior (9% ± 11%) walls. Conclusion: Misregistration of the stress PET/CT dataset leads to significant global and regional artifactual alterations in the estimated MBF. Quantitative error was observed throughout the myocardium and was not confined to those heart regions that extended into the lung on misregistered CT.