Faculty Bibliography

Dual imaging with both contrast enhanced CT scan and PET-CT is recommended for evaluation of lymphoma. We compared the performance in identification and size measurements of involved lymph nodes in FDG-avid lymphomas on the low dose non-contrast enhanced CT of a PET-CT scan with those on a diagnostic contrast enhanced CT scan. The size of FDG-avid lymph nodes was measured in both the short and long axis on both the low dose non-contrast CT of the PET-CT and the contrast enhanced CT by two independent readers. A total of 307 FGD avid lymph nodes were identified in 52 patients. There was no statistically significant differences in the measured size of the nodes on the non-contrast and contrast enhanced scans (p=0.21). Baseline staging and restaging of FDG-avid lymphomas can be performed with one test, PET-CT, without an accompanying contrast enhanced CT scan, with no effect on the measured nodal size.

Objectives Widespread adoption of new imaging technologies requires that diagnostic performance is maintained as technology migrates from expert sites into general use. This Blinded Independent Evaluation (BIE) study was designed to demonstrate that naive readers could be trained to interpret fluciclovine F18 (aka 18F FACBC) images with acceptable diagnostic performance and reproducibility. Methods A reader training program using standardised interpretation methodology was established following an expert consensus meeting facilitated by the SNMMI Clinical Trial Network. The BIE was conducted at the American College of Radiology Clinical Research Centre. 3 independent board-certified radiologists or nuclear medicine physicians were trained and their proficiency assessed, using training and proficiency image sets distinct from those used in the blinded read itself. Fluciclovine F18 PET-CT images (n=121) and corresponding standard of truth data (SoT), from 110 subjects with biochemical relapse of prostate cancer, were collected from Emory University, Atlanta, USA. The images were from a single time-point acquisition undertaken from the symphysis pubis to above the diaphragm starting 5 min post-injection of ~10mCi fluciclovine F18 and were acquired on a GE DLS (2D) or GE D690 (3D). The readers evaluated the images in a random sequence blinded to clinical data. Primary objectives were: i) the diagnostic performance of individual readers and overall interpretation (2/3 reader concordance) compared to SoT (histopathology and/or clinical follow-up); ii) inter-reader reproducibility. Analyses were conducted at Lesion, Region (Prostate {including bed} or Extra-Prostatic) and Subject level. Secondary objectives included comparison to the expert reader at Emory and assessment of intra-reader reproducibility. Results Table 1 shows the diagnostic performance results by reader and overall interpretation on a regional basis, using the composite SoT (histopathology and clinical follow up). The lower specificity in the Prostate region is due to the overall low number of patients with true negative disease in this region. Inter-reader agreement amongst the three readers was 94.7% , 74.4%, 70.3% for the Lesion, Prostate and Extra-Prostatic regions, respectively, with associated Fleiss' Kappa values of 0.54, 0.50 and 0.57. Intra-reader agreement was 97.8%, 96.9%, 99.1% at the Lesion level, 100%, 100%, 91.7% for the Prostate region and 83.3%, 75.0%, 83.3% for the Extra-Prostatic region. The degree of agreement between the blinded read and the on-site read of the fluciclovine F18 scans was 95.4%, 95.4% , 94.2% at the Lesion level, 90.9%, 90.1%, 76.9% for the Prostate region, 81.8%, 82.6%, 76.9% for the Extra-Prostatic region. Conclusions Use of standardised interpretation methodology and a specific training program for the assessment of fluciclovine F18 PET-CT images enables naive readers to achieve good diagnostic performance and reproducibility when staging recurrent prostate cancer patients. These finding support the wider dissemination of this technology in the future. (Table Presented)

(18)F-fluorodeoxyglucose positron emission tomography with (FDG-PET) has a well-established role in the pre- and post-treatment staging of Hodgkin lymphoma (HL), however its use as a predictive therapeutic tool via responded-adapted therapy continues to evolve. There have been a multitude of retrospective and noncontrolled clinical studies showing that early (or interim) FDG-PET is highly prognostic in HL, particularly in the advanced-stage setting. Response-adapted treatment approaches in HL are attempting to diminish toxicity for low-risk patients by minimizing therapy, and conversely, intensify treatment for high-risk patients. Results from phase III noninferiority studies in early-stage HL with negative interim FDG-PET that randomized patients to chemotherapy alone versus combined modality therapy showed a continued small improvement in progression-free survival for patients who did not receive radiation. Preliminary reports of data escalating therapy for positive interim FDG-PET in early-stage HL and for de-escalation of therapy [i.e. bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP)] for negative interim FDG-PET in advanced stage HL (i.e. deletion of bleomycin) have demonstrated improved outcomes. Maturation of these studies and continued follow up of all response-adapted studies are needed. Altogether, the treatment of HL remains an individualized clinical management choice for physicians and patients. Continued refinement and optimization of FDG-PET is needed, including within the context of targeted therapeutic agents. In addition, a number of new and novel techniques of functional imaging, including metabolic tumor volume and tumor proliferation, are being explored in order to enhance staging, characterization, prognostication and ultimately patient outcome.

UNLABELLED:Our objective was to determine whether early change in standardized uptake values (SUVs) of 3'deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. METHODS:This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent (18)F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. RESULTS:Fifty-one of 90 recruited patients (median age, 54 y; stage IIA-IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31-46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50-0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). CONCLUSION/CONCLUSIONS:(18)F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy (18)F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of (18)F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test (18)F-FLT PET in a more uniformly treated patient population.

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

INTRODUCTION/BACKGROUND:There is uncertainty about accuracies of dual-phase (DP) and dual-tracer (DT) parathyroid scintigraphy with the newly added SPECT/CT. Although SPECT/CT was shown to be helpful in parathyroid adenoma (PA) localization, it may not have optimal resolution as pinhole. This study directly compared diagnostic accuracies and confidences of various imaging protocols on same patients. PATIENTS AND METHODS/METHODS:One hundred fifty-five patients with pathologically confirmed diagnosis were included. Pinhole DP, pinhole DT, pinhole DP SPECT/CT, pinhole DT SPECT/CT, and SPECT/CT with only pinhole-delayed MIBI (D) were reviewed for accuracies and certainties of PA diagnosis/localization. Parathyroid adenomas were classified as clearly or unclearly distinguishable from thyroid. Furthermore, the contribution of pinhole DP to pinhole DT SPECT/CT was assessed. RESULTS:Of 153 PAs, the correct diagnosis/localization was significantly higher by pinhole DT SPECT/CT than pinhole DP SPECT/CT, SPECT/CT D, pinhole DT alone, and DP alone. Parathyroid adenomas were clearly more distinguished from thyroid in pinhole DT than DP with/without SPECT/CT. Consequently, PA diagnosis certainty was higher in pinhole DT than DP, whereas PA localization certainty was higher in both with SPECT/CT. In pinhole DT SPECT/CT, the pinhole DP addition confirmed diagnosis/localization of only 24 uncertain PAs. CONCLUSIONS:In this large patient group, the accuracy and certainty of PA diagnosis/localization were higher in pinhole DT SPECT/CT than all other parathyroid scintigraphy protocols. Pinhole DT better identified PA than pinhole DP, whereas SPECT/CT improved PA localization in both protocols. Pinhole DP showed limited contribution and thus should be only considered when PA diagnosis/localization is uncertain by pinhole DT SPECT/CT.