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Segmentation of lymphoma lesions in FDG PET/CT images is critical in both assessing individual lesions and quantifying patient disease burden. Simple thresholding methods remain common despite the large heterogeneity in lymphoma lesion location, size, and contrast. Here, we assess 11 automated PET segmentation methods for their use in two scenarios: individual lesion segmentation and patient-level disease quantification in lymphoma. Lesions on 18 F-FDG PET/CT scans of 90 lymphoma patients were contoured by a nuclear medicine physician. Thresholding, active contours, clustering, adaptive region-growing, and convolutional neural network (CNN) methods were implemented on all physician-identified lesions. Lesion-level segmentation was evaluated using multiple segmentation performance metrics (Dice, Hausdorff Distance). Patient-level quantification of total disease burden (SUV total ) and metabolic tumor volume (MTV) was assessed using Spearman's correlation coefficients between the segmentation output and physician contours. Lesion segmentation and patient quantification performance was compared to inter-physician agreement in a subset of 20 patients segmented by a second nuclear medicine physician. In total, 1223 lesions with median tumor-to-background ratio of 4.0 and volume of 1.8 cm 3 , were evaluated. When assessed for lesion segmentation, a 3D CNN, DeepMedic, achieved the highest performance across all evaluation metrics. DeepMedic, clustering methods, and an iterative threshold method had lesion-level segmentation performance comparable to the degree of inter-physician agreement. For patient-level SUV total and MTV quantification, all methods except 40% and 50% SUV max and adaptive region-growing achieved a performance that was similar the agreement of the two physicians. Multiple methods, including a 3D CNN, clustering, and an iterative threshold method, achieved both good lesion-level segmentation and patient-level quantification performance in a population of 90 lymphoma patients. These methods are thus recommended over thresholding methods such as 40% and 50% SUV max , which were consistently found to be significantly outside the limits defined by inter-physician agreement.

Lymphoma is a potentially curable disease; however, the clinical challenge lies in further improvement of outcomes. PET with fludeoxyglucose is an effective imaging tool. PET-derived quantitative metrics have raised significant interest to be used as a prognostic factor to complement clinical parameters for treatment decisions. The most optimized use of these quantitative PET metrics, however, will be possible with the standardization of imaging procedures. In this article, we review the technical and methodological considerations related to PET-derived quantitative metrics, and the relevant published data to emphasize the potential value of these metrics in patient prognosis and treatment response in lymphoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although visual assessment using the Deauville criteria is strongly recommended by guidelines for treatment response monitoring in all FDG-avid lymphoma histologies, the high rate of false-positives and concerns about interobserver variability have motivated the development of quantitative tools to facilitate objective measurement of tumor response in both routine and clinical trial settings. Imaging studies using functional quantitative measures play a significant role in profiling oncologic processes. These quantitative metrics allow for objective end points in multicenter clinical trials. However, the standardization of imaging procedures including image acquisition parameters, reconstruction and analytic measures, and validation of these methods are essential to enable an individualized treatment approach. A robust quality control program associated with the inclusion of proper scanner calibration, cross-calibration with dose calibrators and across other scanners is required for accurate quantitative measurements. In this section, we will review the technical and methodological considerations related to PET-derived quantitative metrics and the relevant published data to emphasize the potential value of these metrics in the prediction of patient prognosis in lymphoma., (Copyright © 2017. Published by Elsevier Inc.)

Interim and end-of-treatment PET/CT have become central to the evaluation of Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical decision making by providing an overview of available data on the diagnostic and prognostic value of PET/CT imaging for response assessment and pretransplant evaluation in lymphoma. The relative strengths and limitations of these techniques in various disease subtypes and clinical scenarios are explored, along with their current standards for reporting and latest developments. Particular attention is given to response-adapted therapy, which is emerging as a cornerstone of clinical management., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Lymphoid malignancies are a heterogeneous group of tumors that have distinctive clinical and biological behaviors. The increasing prevalence of disease reflects both treatment advances and the fact that some of these tumors are indolent. The ability to determine treatment needs at diagnosis remains problematic for some of the tumors, such as in follicular lymphomas. Major clinical advances will likely depend on precision oncology that will enable identification of specific disease entities, prognostic determination at diagnosis, and identification of precise therapeutic targets and essential pathways. However, refinement in diagnostic evaluation is an evolving science. The ability to determine prognosis at diagnosis is variable, and for many of the lymphoid malignancies prognosis can only be made after initial treatment. Clinical trials that aim to evaluate specific features of these diseases are required in order to advance clinical practice that meaningfully addresses this important public health challenge. Herein, we describe the process and general recommendation from the National Cancer Institute (NCI) clinical trials planning meeting in November 2014 to address clinical trial design and biomarker proposals in the context of NCI-supported lymphoma clinical trials in the National Clinical Trials Network., (Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.)

The effectiveness of cancer therapy, both in individual patients and across populations, requires a systematic and reproducible method for evaluating response to treatment. Early efforts to meet this need resulted in the creation of numerous guidelines for quantifying posttherapy changes in disease extent, both anatomically and metabolically. Over the past few years, criteria for disease response classification have been developed for specific cancer histologies. To date, the spectrum of disease broadly referred to as lymphoma is perhaps the most common for which disease response classification is used. This review article provides an overview of the existing response assessment criteria for lymphoma and highlights their respective methodologies and validities. Concerns over the technical complexity and arbitrary thresholds of many of these criteria, which have impeded the long-standing endeavor of standardizing response assessment, are also discussed., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

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.

Purpose: Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely., Methods: An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma., Results: A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods., Conclusion: This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

The management approach in Hodgkin's (HL) and high-grade non-Hodgkin's lymphomas (NHL) has shifted towards reducing the toxicity and long-term adverse effects associated with treatment while maintaining favorable outcomes in low-risk patients. The success of an individualized treatment strategy depends largely on accurate diagnostic tests both at staging and during therapy. In this regard, positron emission tomography (PET) using fluorodeoxyglucose (FDG) with computed tomography (CT) has proved effective as a metabolic imaging tool with compelling evidence supporting its superiority over conventional modalities, particularly in staging and early evaluation of response. Eventually, this modality was integrated into the routine staging and restaging algorithm of lymphomas. This review will summarize the data on the proven and potential utility of PET/CT imaging for staging, response assessment, and restaging, describing current limitations of this imaging modality.

Purpose: To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials., Methods: An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted., Recommendations: PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.

Positron emission tomography (PET) imaging using [F-18]fluorodeoxyglucose (FDG) has become a useful imaging modality in the staging and treatment evaluation algorithm for lymphoma, providing unique metabolic information. Increased FDG uptake in lymphoma tumor masses is a function of increased anaerobic metabolism and longer residence time of FDG in malignant cells relative to most normal tissues. The information provided by FDG-PET appears to result in greater sensitivity compared to anatomic imaging modalities, particularly computed tomography (CT). Over several decades CT has been the principal imaging modality for the staging and restaging of lymphoma, although it can have significant shortcomings stemming from its sized-based criteria, particularly in the post-therapy setting. Gallium-67 (Ga-67) scintigraphy has played an important role in monitoring response to therapy; however, the sensitivity of Ga-67 depends on histologic subtype of lymphoma, size, and location of disease. Published results suggest that FDG-PET is superior to Ga-67 imaging and equal or superior to CT for the detection of nodal and extranodal lymphoma at initial staging. Furthermore, persistent FDG uptake during and after chemotherapy has a high sensitivity and specificity for prediction of subsequent relapse. While in some cases FDG-PET imaging can yield findings that prompt a change in treatment strategy, prospective studies are necessary to better establish the ability of routine FDG-PET imaging to impact therapeutic outcomes for patients with lymphoma.

PET is a unique form of diagnostic imaging that observes in vivo biologic changes using radiopharmaceuticals that closely mimic endogenous molecules. (18)F-FDG, which allows the evaluation of glucose metabolism, is the most commonly used tracer in oncology because of the practical half-life of (18)F (110 min), compared with other short-lived positron emitters. (18)F-FDG uptake in tumors is proportional to the glycolytic metabolic rate of viable tumor cells indicating the increased metabolic demand of tumors for glucose. (18)F-FDG PET significantly improves the accuracy of imaging tumors in initial staging, management of recurrent cancer, and monitoring of therapy response. The information provided by this technique is more sensitive and specific than that provided by anatomic imaging modalities. (18)F-FDG PET is particularly superior to CT or MRI in the ability to evaluate the effectiveness of various treatment regimens early during therapy or after therapy. In this review, we discuss the role of (18)F-FDG PET in evaluating the response to therapy and the impact of this information on patient management.

Positron emission tomography (PET) imaging has become a very useful technique for staging and monitoring therapy response in lymphoma, providing unique information about the biological behavior of disease. Increased fluorine-18 fluorodeoxyglucose (FDG) uptake in lymphoma is based on elevated glycolysis and longer residence time of FDG in malignant cells compared with most normal tissues. The metabolic information provided by this technique suggests that FDG-PET may be more sensitive than the anatomical imaging modalities. Computed tomography (CT) is the principal imaging modality for the staging and restaging of lymphoma. Nonetheless, this technique has significant shortcomings, particularly in the post-therapy setting. Gallium-67 scintigraphy has played an important role in monitoring response to therapy and follow-up of patients; however, the sensitivity of 67Ga depends on the subtype of lymphoma and the size and location of disease. Published results strongly indicate that FDG-PET is superior to 67Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma.

With the advent of positron emission tomography (PET), metabolic imaging has become a reality for tumor staging and monitoring response to therapy in lymphoma. Increased Fluorine-18 fluorodeoxyglucose ([(18)F]FDG) uptake in lymphomas has been well documented in the literature; it is based upon elevated glycolysis and longer residence time of FDG in malignant cells compared to most normal tissues. This suggests that in tumor staging, FDG-PET may be more sensitive and specific than the anatomic imaging modalities. Computed tomography (CT) is the standard imaging modality for the staging and restaging of lymphoma, and Gallium-67 ((67)Ga) scintigraphy has played an important role in monitoring response to therapy and follow-up of patients. Published results suggest that FDG-PET is superior to (67)Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma.