Faculty Bibliography

A significant amount of data has been published over the past decade regarding the clinical utility of F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and management of Hodgkin lymphoma (HL). This includes studies examining interim FDG-PET, which has been shown to be a strong tool for predicting relapse and survival, especially in advanced- stage HL. Despite progress, a number of questions remain regard- ing the precise role and value of FDG-PET in the diagnosis, risk stratification, and management of HL. These questions include the need for concomitant contrast enhanced computed tomography with FDG-PET, reproducibility and interpretability of FDG-PET, optimal imaging for the treatment surveillance of HL following definitive treatment, and the use of FDG-PET for patients with relapsed/refractory disease, including stem cell transplantation. In this review, these issues are critically examined and the study designs and results of observational and prospective FDG-PET response-adaptive clinical trials in HL are described in detail. In addition, novel techniques and future applications of FDG- PET, such as metabolic tumor volume, tumor proliferation via 3'-deoxy-3'-18F-fluorothymidine, and integrated PET/magnetic resonance imaging are discussed.

BACKGROUND:Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL. METHODS:Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for 4 induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by computed tomography was correlated with clinical risk factors, [18F]fluorodeoxyglucose positron emission tomography findings at week 3, Fcγ polymorphisms, immunohistochemical markers, and statin use. RESULTS:Therapy was well-tolerated, with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (42.4%) and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (P = .022). CONCLUSIONS:The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemoimmunotherapies and further support the development of biologic, nonchemotherapeutic approaches for these patients.

Lymphomas are heterogeneous but potentially curable group of neoplasms. Treatment of lymphomas has rapidly evolved overtime with significant improvement in the cure rate and reductions in treatment-related toxicities. Despite excellent results, treatment programs are continued to be developed to achieve better curative and safety profiles. In these patients individualized therapy schemes can be devised based on a well-defined risk categorization. The therapy efficacy can be increased early during therapy in non-responding patients with escalated therapy protocols or with the addition of radiation therapy, particularly, in advanced-stage or unfavorable risk patients. The increasing availability of positron emission tomography using 18F-fluorodeoxyglucose, particularly fused with computed tomography (FDG-PET/CT) has lead to the integration of this modality into the routine staging and restaging for lymphoma with convincing evidence that it is a more accurate imaging modality compared with conventional imaging techniques. FDG-PET/CT is also is a promising surrogate for tumor chemosensitivity early during therapy. This review will summarize published data on the utility of FDG-PET/CT imaging in the staging, restaging, and predicting therapy response in patients with lymphoma.

BACKGROUND:Foot ulcer with suspected infection is one of the most common reasons for hospitalization and a major factor contributing to morbidity and high healthcare-related expenses among diabetic patients. Many patients will require amputation; however, major amputation is associated with an alarmingly high 5-year mortality rate. In this study, we assess the diagnosis and management of suspected foot infection in diabetic patients using dual-isotope (DI) single-photon emission computed tomography/computed tomography (SPECT/CT) compared with conventional imaging. METHODS:The diagnostic accuracy in and management of 227 patients who had undergone DI SPECT/CT was compared with that of 232 similar patients who had undergone conventional imaging including plain radiography, CT, planar bone scanning, planar indium-111 white blood cell scanning, and MRI. The duration of hospitalization was additionally compared between these two groups of patients after excluding patients with other active comorbidities. RESULTS:Soft-tissue infection, osteomyelitis with or without soft-tissue infection, and other bony pathologies were more accurately and confidently identified with DI SPECT/CT than with conventional imaging. DI SPECT/CT use was associated with significantly fewer major amputations and more selective bony resection as well as with shorter duration of hospitalization when compared with conventional imaging. CONCLUSION/CONCLUSIONS:In this large population of diabetic patients with suspected foot infection DI SPECT/CT was more accurate in diagnosing and localizing infection compared with conventional imaging. In addition, DI SPECT/CT provided clear guidance and promoted many limb salvage procedures. Of equal importance to health economics, DI SPECT/CT use was associated with considerably reduced length of hospitalization compared with conventional imaging.

Preoperative systemic therapy with cytotoxic or biologic anticancer regimens has gained significant popularity in the management of breast cancer. Moreover, there is a worldwide paradigm shift toward an individualized approach to identify predictive surrogate markers for stratifying patients into distinct subgroups to improve outcome after neoadjuvant or adjuvant therapy. Although achievement of pathologic complete response constitutes the gold standard for assessing therapeutic efficacy only a minority of patients achieve a pathologic complete response. Imaging has evolved to play a crucial role in monitoring treatment effectiveness, particularly, early during therapy. There is mounting evidence that (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a more superior metabolic imaging modality than anatomic modalities for assessment of the response during or at completion of treatment. Ultimately, the prediction of therapeutic effectiveness or survival or both by FDG-PET imaging could successfully tailor treatment and avoid unnecessary toxicities. This paper provides an overview of current use and the main indications of FDG-PET and integrated PET/computed tomography in response assessment of breast cancer as well as the future directions for the management using non-FDG-based tracers developed against specific targets.

Hodgkin lymphoma (HL) is a curable disease with currently available chemotherapy regimens. Major late morbidities can potentially be avoided in most limited-stage HL patients if the treatment can be adapted to the patient's early response profile. The therapy efficacy can also be increased early during therapy in nonresponding HL patients with the addition of involved-field radiation therapy or a switch to an escalated therapy protocol, particularly in advanced-stage or unfavorable-risk patients. (18)F-FDG PET is a well-established surrogate for tumor chemosensitivity early during therapy. The ongoing PET-adaptive clinical trials are testing the hypothesis that a decision can reliably be made on escalating or deescalating therapy based on interim PET results. Discussed in this review is the integral role of interim (18)F-FDG PET in HL, challenges, critical issues to improve its accuracy, and the observations from completed interim PET studies and ongoing PET-adaptive clinical trials.

UNLABELLED:At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. METHODS:A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. RESULTS:Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P < 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf α. CONCLUSION/CONCLUSIONS:The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.

Despite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria. A final remark on the appropriate use of interim PET is also provided.

Our objective was to validate the International Harmonization Project (IHP) positron emission tomography (PET) response criteria and correlate with the Deauville criteria and diagnostic computed tomography-based (dCT) lesion size changes. All patients were recruited prospectively to the Cancer and Leukemia Group B (CALGB) 50203 trial for the treatment of stage I-II, non-bulky Hodgkin lymphoma (HL). [(18)F]Fluorodeoxyglucose (FDG) PET and dCT were performed at baseline and after two doxorubicin, vinblastine and gemcitabine (AVG) cycles (PET-2, dCT-2) in 88 patients. IHP and Deauville criteria and percent decrease in the sum of the products of the perpendicular diameters (%SPPD) after two cycles were correlated with progression-free survival (PFS). After a median follow-up of 3.3 years, 23.9% of patients relapsed/progressed (3-year PFS 77%). By IHP, the 2-year PFS was 88% and 54% for PET-2 negative and positive groups, respectively (p = 0.0009). Similar results were obtained for Deauville criteria. In a univariate analysis, PET-2 predicted PFS better than %SPPD, and in a combinatorial analysis, in the PET-2 positive group, a negative dCT-2 increased PFS by 27-35%. However, some confidence intervals were large due to small sample sizes. In conclusion, IHP and Deauville criteria-based interpretation of PET-2 was strongly associated with 2-year PFS. The combined analysis of PET-2 with dCT-2 suggested a better predictive value for PFS compared to either test alone. Further studies are under way to confirm these findings.