RESISTing the Need to Quantify: Putting Qualitative FDG-PET/CT Tumor Response Assessment Criteria into Daily Practice

Abstract

Tumor response assessments are essential to evaluate cancer treatment efficacy and prognosticate survival in patients with cancer. Response criteria have evolved over multiple decades, including many imaging modalities and measurement schema. Advances in FDG-PET/CT have led to tumor response criteria that harness the power of metabolic imaging. Qualitative PET/CT assessment schema are easy to apply clinically, are reproducible, and yield good prognostic results. We present 3 such criteria, namely, the Lugano classification for lymphoma, the Hopkins criteria, and the Neck Imaging Reporting and Data Systems criteria for head and neck cancers. When comparing baseline PET/CTs with interim or end-of-treatment PET/CTs, radiologists can classify the tumor response as complete metabolic response, partial metabolic response, no metabolic response, or progressive disease, which has important implications in directing further cancer management and long-term patient prognosis. The purpose of this article is to review the progression of tumor response assessments from CT- and PET/CT-based quantitative and semi-quantitative systems to PET/CT-based qualitative systems; introduce the classification schema for these systems; and describe how to use these rapid, powerful, and qualitative PET/CT-based systems in daily practice through illustrative cases.

Fig 1.

The D5PS scores of lesions qualitatively based on the FDG uptake relative to the mediastinal blood pool (MBP) and hepatic parenchymal FDG activity. The figure demonstrates hypothetical masses (arrows) and their FDG uptake relative to the MBP and liver activity. D5PS score of 1 for a left axillary mass with FDG uptake no greater than background activity. D5PS score of 2 for cervical mass with FDG uptake above background but less than MBP or liver. D5PS score of 3 for hilar mass with FDG uptake greater than MBP but less than or equal to the hepatic activity. A D5PS score of 4 for a mass in right lung base with FDG uptake greater than both MBP and liver. A D5PS score of 5 for a midabdominal mass with FDG uptake markedly greater than that of the liver.

Fig 2.

A partial metabolic response and CMR based on Lugano criteria. A 47-year-old man with diffuse large B-cell lymphoma demonstrates (A) baseline intense FDG avidity in mediastinal (MIP and PET/CT of the chest [arrows denote a large pericardial lymph node conglomerate]) and bilateral levels III and IV lymphadenopathy (PET/CT of the neck [arrow denotes a large level III node]), a D5PS score of 5. Incidentally, on the PET/CT of the neck, the arrowhead denotes a dysfunctional right vocal cord, likely due to disease impacting the ipsilateral recurrent laryngeal nerve. B, Interim imaging demonstrates reduced but persistent FDG uptake (2 times greater than the liver) in the retrosternal, pericardial mass (MIP and PET/CT of the chest [arrows]), consistent with a D5PS score of 5 but a Lugano designation of a partial metabolic response. There was interval resolution of the cervical lymphadenopathy. C, End-of-treatment imaging shows a residual pericardial mass on CT (arrow), without FDG uptake above background, consistent with a D5PS score of 1 and a Lugano designation of CMR.

Fig 3.

A posttreatment D5PS score of 5 but partial metabolic response based on Lugano criteria. Baseline imaging demonstrates diffuse lymphadenopathy, including cervical levels II–IV, axillary, mediastinal, abdominal periaortic/pericaval, and right greater than left iliac chains, with intense FDG avidity (arrows), consistent with a D5PS score of 5. Interim imaging during treatment demonstrates significantly reduced size and FDG avidity of the cervical, axillary, and mediastinal lymphadenopathy (arrows), now predominantly limited to the periaortic/pericaval regions and right greater than left iliac chains. The lymph nodes still have FDG avidity markedly greater than mediastinal blood pool and liver, consistent with a D5PS score of 5, but the reduction in size, number, and intensity results in a Lugano designation of a partial metabolic response.

Fig 4.

Hopkins criteria score of 5 in right tonsillar squamous cell carcinoma, consistent with residual tumor. A 71-year-old man with right tonsillar squamous cell carcinoma. MIP from baseline PET/CT demonstrates a Hopkins criteria score of 5 in the primary right tonsillar tumor (arrow) and right greater than left level II–IV cervical lymph nodes (arrowheads). Examination after radiation and chemotherapy shows resolution of the right tonsillar FDG uptake (arrow) and some of the cervical lymph nodes but persistent, focal, and intense FDG uptake in 2 ipsilateral level III and IV lymph nodes (arrowheads); a Hopkins criteria score of 5 is consistent with residual tumor.

Fig 5.

Hopkins criteria score of 2 and NI-RADS score of 1 in right tonsillar squamous cell carcinoma, consistent with a CMR. A 71-year-old man with an intensely FDG-avid right tonsillar squamous cell carcinoma (dotted circle) on pretreatment PET/CT. After treatment, the mass has resolved, with FDG uptake in the region just above the adjacent right internal jugular vein (arrowhead) but similar to the surrounding oropharyngeal soft tissues, consistent with a Hopkins criteria score of 2 and an NI-RADS score of 1 at the primary site. By using Hopkins or NI-RADs criteria, the findings are consistent with an overall CMR.

Fig 6.

An NI-RADS score of 2a in left tonsillar squamous cell carcinoma (SCCa) after chemoradiation, consistent with a Hopkins criteria score of 3 and posttreatment inflammation. A 63-year-old man with a history of left tonsillar SCCa. A, Baseline oblique MIP shows markedly hypermetabolic primary left tonsillar SCCa (arrow). After completion of chemoradiation therapy, repeated FDG PET/CT was obtained. B, Oblique MIP and axial PET/CT show residual hypermetabolic mucosal activity of moderate intensity (arrow) throughout the tonsil bed. The findings are compatible with NI-RADS 2a. Linked management recommendations in the NI-RADS criteria suggest correlation with direct visualization given that such a finding typically represents non-neoplastic FDG uptake. As a comparison, the FDG uptake is greater than the liver and much greater than the internal jugular vein, this is consistent with a Hopkins criteria score of 3. The findings suggest benign posttreatment inflammation. Lesions with this score can be false-negatives and demonstrate intermediate overall survival and progression-free survival compared with scores of 1–2 and 4–5. Due to the false-negative probability, these lesions should be biopsied before altering the treatment plan.