MRI and PET/MRI in hematologic malignancies

The role of MRI differs considerably between the three main groups of hematological malignancies: lymphoma, leukemia, and myeloma. In myeloma, whole-body MRI (WB-MRI) is recognized as a highly sensitive test for the assessment of myeloma, and is also endorsed by clinical guidelines, especially for detection and staging. In lymphoma, WB-MRI is presently not recommended, and merely serves as an alternative technique to the current standard imaging test, [18F]FDG-PET/CT, especially in pediatric patients. Even for lymphomas with variable FDG avidity, such as extranodal mucosa-associated lymphoid tissue lymphoma (MALT), contrast-enhanced computed tomography (CT), but not WB-MRI, is presently recommended, despite the high sensitivity of diffusion-weighted MRI and its ability to capture treatment response that has been reported in the literature. In leukemia, neither MRI nor any other cross-sectional imaging test (including positron emission tomography [PET]) is currently recommended outside of clinical trials. This review article discusses current clinical applications as well as the main research topics for MRI, as well as PET/MRI, in the field of hematological malignancies, with a focus on functional MRI techniques such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, on the one hand, and novel, non-FDG PET imaging probes such as the CXCR4 radiotracer [68Ga]Ga-Pentixafor and the amino acid radiotracer [11C]methionine, on the other hand. Level of Evidence: 5. Technical Efficacy Stage: 3

Is local review of positron emission tomography scans sufficient in diffuse large B-cell lymphoma clinical trials? A CALGB 50303 analysis

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS). METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. RESULTS: Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (\u3c66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. CONCLUSIONS: These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials

Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer

Background: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. Methods: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. Results: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. Conclusions: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients. Trial registration: ClinicalTrials.gov NCT0058827

PET imaging for response assessment in lymphoma: potential and limitations

Fluorodeoxyglucose positron emission tomography (FDG-PET) is now considered the most accurate tool for the assessment of treatment response and prognosis in patients with Hodgkin lymphoma and aggressive non-Hodgkin lymphoma. This article discusses the potential and limitations of FDG-PET for response assessment in malignant lymphoma during chemotherapy (interim PET) and at the end of chemotherapy. Interim PET is used to predict the likelihood for a complete response at the end of such therapy. End-of-treatment PET aims to establish the completeness of response or the presence of residual viable tumor tissue. Until the results of ongoing clinical trials emerge over the next 5 years, interim PET should be considered investigational and should not be used for patient management outside of study protocols

Current status of the role of PET imaging in diffuse large B-cell lymphoma

PET-CT (positron emission tomography-computed tomography) has emerged as an indispensable tool in the management of patients with diffuse large B-cell lymphoma (DLBCL). It is the standard imaging test for initial staging and is superior to CT in determining remission status and has replaced CT in this regard. The focus of this seminar will highlight controversial aspects on the role of PET-CT in the treatment of patients with DLBCL and will address the following questions: 1) Is a contrasted enhanced CT scan necessary for initial staging in the PET era? 2) Is a bone marrow biopsy required for initial staging of DLBCL in the era of PET imaging? 3) What is the role of interim PET in management? 4) Should PET scans be used for surveillance in patients in remission? 5) What is the role of semiquantitative PET and CT metrics in prognostication and response assessment

Comparing the clinical performance and cost efficacy of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in the diagnosis of recurrent prostate cancer: a Markov chain decision analysis.

PURPOSE Amongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address. METHODS Two hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use. RESULTS The PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66-0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99-1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82-1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was - 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark). CONCLUSION The analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers

Solitary Extramedullary Plasmacytoma of the Cricoid Cartilage—Case Report

Solitary plasmacytoma (SP) is an extremely rare form of hematologic malignancy that can be classified as solitary bone plasmacytoma or solitary extramedullary plasmacytoma. Here, we report a patient who presented with progressive shortness of breath and foreign body sensation in his throat. Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) demonstrated an abnormal FDG-avid soft tissue mass arising from the larynx involving the cricoid cartilage without additional suspicious lesions. Histology revealed an abundance of plasma cells; immunohistochemistry was positive for CD138 expression and lambda chains, and negative for CD20. Comprehensive imaging studies and panendoscopy of the ENT tract confirmed solitary disease involvement. Following additional systemic work-up, a diagnosis of extramedullary plasmacytoma was rendered. The patient underwent definitive radiotherapy using intensity-modulated radiation therapy (total dose of 46 Gy, divided in 23 fractions of 200 cGy). Serial PET/CT showed the stepwise resolution of abnormal FDG uptake and resolution of the cricoid cartilage lesion. With 22 months of follow-up, the patient remains free of disease. We describe the rare case of SP presenting as a FDG-avid hypermetabolic soft tissue mass in the cricoid cartilage, which should be considered in the differential diagnosis of laryngeal tumors. Of note, SP is radiosensitive; favorable outcome can be expected once treated with doses of 40–50 Gy. FDG PET/CT is helpful in diagnosis and response assessment for this disease