Impact of local tumor-to-background uptake ratio on PET metabolic response assessment.

IntroductionFluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is used for non-invasive staging and restaging of solid malignant tumors. PET-CT based criteria have been developed to evaluate the response to targeted therapy. These include the European Organization for Research and Treatment of Cancer (EORTC) and the PET Response Criteria in Solid Tumors (PERCIST). The aim of this study was to determine the agreement between EORTC and PERCIST criteria for treatment response evaluation in patients with solid malignant tumors.Materials and methodsThis was a retrospective study conducted from February 2017 till July 2017. Electronic medical records of patients diagnosed with solid malignant tumors were searched. Experienced radiologists evaluated the PET-CT images based on EORTC and PERCIST criteria. The Kappa (κ) test was used for evaluation of agreement between treatment response according to EORTC and PERCIST criteria.ResultsOut of 54 patients, 41 (75.9%) were male and 13 (24.1%) were female with a mean age of 57.09 ± 10.65 years. According to EORTC criteria, complete metabolic response (CMR) was seen in five (9.3%) of patients, partial metabolic response (PMR) was seen in 36 (66.7%) of patients, progressive metabolic disease (PMD) was seen in nine (16.7%) of patients and stable metabolic disease (SMD) was seen in four (7.4%) of patients. According to PERCIST criteria, CMR was seen in five (9.3%) of patients, PMR was seen in 33 (61.1%) of patients, PMD was seen in nine (16.7%) of patients and SMD was seen in seven (13.0%) of patients. EORTC and PERCIST agreed on 43 (79.6%) of the patients with κ-coefficient of 0.62 indicating good agreement (p-value of <0.001).ConclusionEORTC and PERCIST criteria have a good agreement in evaluating treatment response in solid malignant tumors. Therefore, adoption of EORTC or PERCIST in PET-CT reporting can standardize the evaluation of oncological treatment results.

317 Background: This study investigates whether changes in 18F-FDG-PET/CT correlate with response to cabozantinib at an early time point (4 wks) versus the conventional time point of restaging (8 wks) in pts with mUC, using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Methods: 68 pts with mUC in a single arm phase II clinical trial of cabozantinib underwent FDG-PET/CT scans at baseline, 4 and 8 wks. Up to 5 lesions with the highest Standard Uptake Value (SUV) were designated as target lesions. Response was determined using 2 versions of PERCIST (1 lesion vs top 5 lesions with highest FDG uptake) for FDG-PET/CT at 4 and 8 wks. PERCIST response classifications were compared to RECIST v1.1 at 8 wks. Results: 54 pts had evaluable disease. The single lesion 4 wk response by PERCIST showed 40% partial metabolic response (PMR), 33% stable metabolic disease (SMD), and 27% progressive metabolic disease (PMD). The single lesion 8 wk response by PERCIST showed 31% PMR, 31% SMD, and 38% PMD. The single lesion analysis coincided with multiple lesion PERCIST analysis in 86% of pts at 4 wks and 89% at 8 wks. The 4 wk PET/CT was predictive of the 8 wk PET/CT in 75% of single lesion and 76% of multiple lesion analyses. In lesion-based analysis, the 4 wk PET/CT was predictive of the 8 wk PET/CT in 74% of bone, 89% of lung, 77% of lymph node, 74% of soft tissue, and 58% of liver lesions. Only 42% of the 8 wk PERCIST and RECIST classifications coincided. At 8 wks, 40% showed response in FDG PET-CT restaging vs 7% complete/partial response by RECIST. Conclusions: The 4 wk PET/CT scan predicts the therapy response at the 8 wk PET/CT scan however the 4 wk scan overestimates the 8 wk response. The single lesion analysis by PERCIST correlates with the multiple lesion analysis and may have more clinical utility. In the lesion-based analysis, the 4 wk PET/CT scan is predictive of the 8 wk PET/CT for bone, lung, lymph node and soft tissue but not for liver lesions. Response classifications by PERCIST are not in agreement with response classifications by RECIST. Although the methods may be complementary, they are not interchangeable. Further studies are required to validate these findings. Clinical trial information: NCT01688999.

Although the term mixed metabolic response is commonly used in PET/CT reports, it should be a red flag to reconsider the assumptions made by the PET scan reader. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is recognized as an accurate imaging method for detecting response to cancer therapies. Critical clinical decisions regarding therapy are dependent on accurate interpretation of findings. The use of standardized terminology for response assessment, such as that in the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), is highly recommended. With PERCIST, treatment response is categorized as complete metabolic response, partial metabolic response, stable metabolic disease, or progressive metabolic disease. Mixed metabolic response is not included in PERCIST. Rather, it is used colloquially to describe a scenario in which scanning performed after systemic cancer therapy reveals divergent findings, with some tumor foci responding and others not responding or even seen progressing. In PERCIST, mixed metabolic response should be described as stable metabolic disease or progressive metabolic disease. However, the PET/CT reader may also wish to suggest that individual tumors have heterogeneous genetic and/or other characteristics and consequently a mixed response to therapy. The concept of tumor heterogeneity is gaining momentum in cancer research and thus possibly leading to options for therapy targeted to oligometastases that are not responding. However, the authors suggest exercising extreme caution when PET/CT findings appear at first to reflect what some might call a mixed response. In addition, they have found that FDG PET/CT findings are often confounding owing to the simultaneous presence of two or more unrelated disease processes. Common examples include synchronous neoplasms, inflammatory processes, and treatment-related effects. Thus, an apparent mixed response is a red flag to reconsider whether all of the FDG-avid findings are actually metastases of the same cancer. Common mimics of a mixed metabolic response that do not represent true tumor heterogeneity are highlighted to improve the FDG PET/CT reader's recognition of these lesions.©RSNA, 2019.

To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the European Organization for Research and Treatment of Cancer (EORTC) criteria and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 using PET volume computer-assisted reading (PET VCAR) for response evaluation in patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy. A total of 35 patients with NSCLC were included in this prospective study. All patients received standard chemotherapy and underwent (18)F-FDG PET/CT scans before and after treatment. With the assistance of PET VCAR, the chemotherapeutic responses were evaluated according to the RECIST 1.1, EORTC criteria and PERCIST 1.0. Concordance among these protocols was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. Progression-free survival (PFS) was calculated using the Kaplan-Meier test. RECIST 1.1 and EORTC response classifications were discordant in 20 patients (57.1%; κ = 0.194, P < 0.05), and RECIST 1.1 and PERCIST 1.0 classifications were discordant in 22 patients (62.9%; κ = 0.139, P < 0.05). EORTC and PERCIST 1.0 classifications were discordant in only 4 patients (11.4%), resulting in better concordance (κ = 0.804, P > 0.05). Patients with a partial remission according to RECIST 1.1 had significantly longer PFS (P < 0.001) than patients with progressive disease, but not significantly longer than patients with stable disease (P = 0.855). According to both the EORTC criteria and PERCIST 1.0, patients with a partial metabolic response had a significantly longer PFS than those with stable metabolic disease and those with progressive metabolic disease (P = 0.020 and P < 0.001, respectively, for EORTC; both P < 0.001 for PERCIST 1.0). EORTC criteria and PERCIST 1.0 are more sensitive and accurate than RECIST 1.1 for the detection of an early therapeutic response to chemotherapy in patients with NSCLC. Although EORTC criteria and PERCIST 1.0 showed similar results, PERCIST 1.0 is preferred because detailed and unambiguous definitions are given. We also found that response evaluations with PERCIST 1.0 using a single lesion and multiple lesions gave similar response classifications.

The purpose of this study was to evaluate therapeutic response to neoadjuvant chemotherapy (NAC) and predict breast cancer recurrence using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Fifty-nine breast cancer patients underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and after NAC prior to planned surgical resection. Pathological complete response (pCR) of the primary tumor was evaluated using PERCIST, while effects of clinicopathological factors on progression-free survival (PFS) were examined using log-rank and Cox methods. Fifty-six patients and 54 primary tumors were evaluated. Complete metabolic response (CMR), partial metabolic response, stable metabolic disease, and progressive metabolic disease were seen in 45, 7, 3, and 1 patients, respectively, and 43, 7, 3, and 1 primary tumors, respectively. Eighteen (33.3%) of the 54 primary tumors showed pCR. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PERCIST to predict pCR were 100% (18/18), 30.6% (11/36), 41.9% (18/43), 100% (11/11), and 53.7% (29/54), respectively. An optimal percent decrease in peak standardized uptake value for a primary tumor corrected for lean body mass (SULpeak) of 84.3% was found to have a sensitivity of 77.8% (14/18), specificity of 77.8% (28/36), PPV of 63.6% (14/22), NPV of 87.5% (28/32), and accuracy of 77.8% (42/54). Seven (12.5%) of the 56 patients developed recurrent disease (median follow-up 28.1months, range 11.4-96.4months). CMR (p = 0.031), pCR (p = 0.024), and early TNM stage (p = 0.033) were significantly associated with longer PFS. PERCIST is useful for predicting pathological response and prognosis following NAC in breast cancer patients. However, FDG-PET/CT showed a tendency toward underestimation of the residual tumor, and relatively low specificity and PPV of PERCIST showed that a combination of other imaging modalities would still be needed to predict pCR.

Introduction: Small cell lung cancer (SCLC) is an aggressive form of lung cancer with poor prognosis. Adequate staging and therapeutic evaluation is necessary for therapy planning. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been shown to be useful for staging and therapy response evaluation. The European Organization for Research and Treatment of Cancer (EORTC) and Positron Emission Tomography Response Criteria In Solid Tumors (PERCIST) criteria were compared in the evaluation of response assessment and prognostic factors were defined in a cohort of SCLC patients. Methods: Twenty-nine consecutive patients with SCLC were included in this study. Sixteen patients had extensive disease and 13 had limited disease. All patients had chemotherapy, 21 had thoracic radiotherapy. FDG-PET/CT scans were performed before and after therapy to evaluate treatment response. Metabolic responses were assessed using the EORTC criteria and PERCIST criteria. Univariate and multivariate analysis were performed using a Cox model to investigate the association between progression-free and overall survival time with a number of covariates. Results: There was perfect concordance between the EORTC and PERCIST criteria. Eight patients had a complete metabolic response (CMR), 9 had a partial metabolic response (PMR), 5 had stable metabolic disease (SMD) and 7 had progressive metabolic disease (PMD). Overall survival time in patients with CMR was significantly longer compared with patients who did not have CMR. The initial or delayed CMR and post-therapeutic standardized uptake value corrected for lean body mass were significantly associated with overall survival. Conclusion: CMR on post-therapeutic FDG-PET/CT in patients with SCLC is an important prognostic factor and may help decision making for therapeutic management.

PurposeTo compare different response criteria using computed tomography (CT) and positron emission tomography (PET) in measuring response and survival in the early phase after programmed death-1 (PD-1) blockade monotherapy in patients with advanced non-small cell lung cancer (NSCLC).MethodsA total of 54 patients with advanced NSCLC who had 2-deoxy-2-[fluorine-18]-fluoro-D-glucose PET or CT at baseline, and 4 and 9 weeks after PD-1 blockade, were registered. Therapeutic response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), the immune-modified RECIST (irRECIST), the PET Response Criteria in Solid Tumors (PERCIST), the immune-modified PERCIST (iPERCIST), and the European Organization for Research and Treatment of Cancer (EORTC) criteria for dichotomous groups, such as responders vs. non-responders and controlled vs. uncontrolled diseases. Cohen’s κ was used to evaluate the concordance among the different criteria.ResultsThe concordance between CT and PET response criteria was fair or slight for responders vs. non-responders, but the agreement between iPERCIST and irRECIST was moderate for controlled vs. uncontrolled diseases. The agreement between EORTC and PERCIST or iPERCIST in detecting responders was higher in the application of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than in the standardized uptake value corrected for lean body mass (SUL)peak. To distinguish controlled from uncontrolled disease, RECIST, irRECIST, and PET criteria (PERCIST, iPERCIST, and EORTC) defined by MTV or TLG were found to be significant predictors of progression-free survival. To distinguish responders from non-responders, iPERCIST by SULpeak or EORTC by TLG were identified as significant indicators. The EORTC criteria using TLG for the detection of responders or uncontrolled diseases had a significantly higher predictive value for response assessment.ConclusionsThe EORTC criteria based on TLG for the early detection of responders and uncontrolled disease were effective as a response assessment at 4 weeks after the PD-1 blockade. When SULpeak was not used but MTV or TLG was, the agreement between EORTC and PERCIST or iPERCIST was almost perfect.

Monitoring Treatment Response to Erlotinib in EGFR-mutated Non–small-cell Lung Cancer Brain Metastases Using Serial O-(2-[18F]fluoroethyl)-L-tyrosine PET

Simple SummaryIn patients with progressive metastatic radioiodine-refractory differentiated thyroid cancer, tyrosine kinase inhibitor (TKI) therapy with lenvatinib improves progression-free survival. Early identification of patients with therapeutic responses to the TKI therapy is clinically relevant due to common side effects and toxicity. The use of metabolic response criteria derived from F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can help to identify those patients who benefit from treatment. In our study, we evaluated different response criteria, namely, the Positron Emission Tomography Response Criteria In Solid Tumors (PERCIST) and European Organization for Research and Treatment of Cancer (EORTC) criteria, to find out which system might be more reliable and suitable in everyday clinical practice. The EORTC criteria could be applied to all patients, and the different PERCIST criteria, in 80% and 88%, respectively. Regarding their survival and treatment responses, patients with a progressive disease could be reliably identified by using all the criteria.Background: We aimed to compare the established metabolic response criteria PERCIST and EORTC for their applicability and predictive value in terms of clinical response assessment early after the initiation of lenvatinib therapy in patients with metastatic radioiodine-refractory (RAI) thyroid cancer (TC). Methods: In 25 patients treated with lenvatinib, baseline and 4-month follow-up F-18 FDG PET/CT images were analyzed using PERCIST 1.0, modified PERCIST (using SUVpeak or SUVmax) and EORTC criteria. Two groups were defined: disease control (DC) and progressive disease (PD), which were correlated with PFS and OS. Results: PERCIST, mPERCIST, PERCISTmax and EORTC could be applied in 80%, 80%, 88% and 100% of the patients based on the requirements of lesion assessment criteria, respectively. With PERCIST, mPERCIST, PERCISTmax and EORTC, the patients classified as DC and PD ranged from 65 to 68% and from 32 to 35%, respectively. Patients with DC exhibited a longer median PFS than patients with PD for EORTC (p < 0.014) and for PERCIST and mPERCIST (p = 0.037), respectively. Conclusion: EORTC and the different PERCIST criteria performed equally regarding the identification of patients with PD requiring treatment changes. However, the applicability of PERCIST 1.0 using SULpeak seems restricted due to the significant proportion of small tumor lesions.

PERCIST in Perspective.

We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in patients with metastatic colorectal cancer and correlated the findings with survival and KRAS status. From 2006 to 2009, patients were included in a phase II trial and treated with cetuximab and irinotecan every second week. They underwent FDG-PET/CT examination at baseline and after every fourth treatment cycle. Response evaluation was performed prospectively according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall responses were registered. Sixty-one patients were eligible for response evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%, stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate 11%. Response agreement was poor, κ-coefficient 0.19. Hazard ratio for overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none had PR but 44% had PMR. In conclusion, morphologic and metabolic response agreement was poor primarily because a large part of the patients shifted from SD with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger fraction of the patients with KRAS mutations had a metabolic treatment response.

The aim of the study was to evaluate PET response criteria in solid tumors (PERCIST) to indicate therapeutic response to definitive chemoradiotherapy, as well as prediction of recurrence and death in patients with esophageal cancer. Before and after recieving definitive chemoradiotherapy, 181 patients with esophageal cancer underwent fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT). PERCIST, reduction rates of tumor uptake and volume of whole lesions, tumor node metastasis (TNM) staging regarding progression-free survival (PFS), and overall survival (OS) were analyzed using log-rank and Cox methods. Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) shown by PERCIST were seen in 42 (23.2%), 113 (62.4%), 14 (7.7%), and 12 (6.6%) patients, respectively. Progression developed in 137 (75.7%) patients and 101 (56.1%) patients died (median follow-up 16.9, range 3.2-124.9 months). Those who achieved CMR showed significantly longer PFS and OS as compared with patients who did not (PMR, SMD, and PMD) (both P < 0.0001). In univariate analysis, initial clinical T status (P = 0.0048), N status (P = 0.011), and TNM stage (P = 0.0006), PERCIST (P < 0.0001), and reduction rate of peak lean body mass standardized uptake value (P < 0.0001), of metabolic tumor volume (P < 0.0001), and of total lesion glycolysis (TLG) (P < 0.0001) were associated with significantly increased OS. Multivariate analysis confirmed PERCIST [hazard ratio (HR): 13.15, 95% confidence interval (CI), 4.54-55.8; P < 0.0001], and TLG reduction rate (HR: 2.21, 95% CI, 1.04-4.68; P = 0.040) as independent OS predictors. PERCIST is useful for evaluating therapeutic response to definitive chemoradiotherapy, and predicting progression and death in patients with esophageal cancer.

To evaluate therapeutic response to chemoradiotherapy and prediction of recurrence and death in patients with head and neck squamous cell carcinoma (HNSCC) using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Forty-two patients (mean 63.4, range 20-79years) with nasopharyngeal (n = 10), oropharyngeal (n = 13), hypopharyngeal (n = 11), or laryngeal (n = 8) cancer underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and approximately 3months (mean 95.0, range 70-119days) after undergoing concurrent chemoradiotherapy. The effect of PERCIST regarding progression-free survival (PFS) and overall survival (OS) was examined using log-rank and Cox methods. Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease shown by PERCIST were seen in 30 (71.4%), 9 (21.4%), 3 (7.1%), and 0 patients, respectively. Fourteen (33.3%) developed recurrent disease (median follow-up 27.2, range 8.7-123.1months) and 9 (21.4%) died (median follow-up 43.6, range 9.6-132.6 months). Furthermore, 4 (13.3%) of 30 patients with CMR developed recurrence, while 7 (77.8%) of 9 with PMR and all 3 (100%) with SMD developed recurrence. Two (6.7%) of 30 patients with CMR, 4 (44.4%) of 9 with PMR, and all 3 (100%) with SMD died. Patients who achieved CMR showed significantly longer PFS and OS as compared to those who did not (PMR and SMD) (both, p < 0.0001). PERCIST is useful for evaluating therapeutic response to chemoradiotherapy and predicting recurrence and death in HNSCC patients.

The study aim was to compare European Organization for Research and Treatment of Cancer (EORTC) criteria with PET Response Criteria in Solid Tumors (PERCIST) for response evaluation of patients with metastatic colorectal cancer treated with a combination of the chemotherapeutic drug irinotecan and the monoclonal antibody cetuximab. From 2006 to 2009, patients with metastatic colorectal cancer were prospectively included in a phase II trial evaluating the combination of irinotecan and cetuximab every second week, as third-line treatment. (18)F-FDG PET/CT was performed between 1 and 14 d before the first treatment and after every fourth treatment cycle until progression was identified by CT with Response Evaluation Criteria in Solid Tumors (RECIST). Response evaluation with (18)F-FDG PET/CT was retrospectively performed according to both EORTC criteria and PERCIST, classifying the patients into 4 response categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Individual best overall metabolic response (BOmR) was registered with both sets of criteria, as well as survival within response categories, and compared. A total of 61 patients and 203 PET/CT scans were eligible for response evaluation. With EORTC criteria, 38 had PMR, 16 had SMD, and 7 had PMD as their BOmR. With PERCIST, 34 had PMR, 20 had SMD, and 7 had PMD as their BOmR. None of the patients had CMR. There was agreement between EORTC criteria and PERCIST in 87% of the patients, and the corresponding κ-coefficient was 0.76. Disagreements were confined to PMR and SMD. Median overall survival (OS) in months with EORTC criteria was 14.2 in the PMR group and 7.2 in the combined SMD + PMD group. With PERCIST, it was 14.5 in the PMR group and 7.9 in the SMD + PMD group. Response evaluation with EORTC criteria and PERCIST gave similar responses and OS outcomes with good agreement on BOmR (κ-coefficient, 0.76) and similar significant differences in median OS between response groups. Compared with EORTC criteria, we find PERCIST unambiguous because of clear definitions and therefore more straightforward to use.

ABSTRACTTherapeutic response to neoadjuvant chemotherapy (NAC) for breast cancer based on Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 with FDG-PET/CT measurements was evaluated, and the results compared to those obtained with currently widely used Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, based on MRI measurements. MRI and FDG-PET/CT examinations were performed in 32 breast cancer patients before and after the NAC prior to a surgical resection. Chemotherapeutic response of the primary tumor and relapse-free survival (RFS) were investigated using RECIST 1.1 and PERCIST 1.0. Pathological complete response (pCR) was seen in 14 (43.8%) patients, while complete response (CR) was noted in 5, partial response in 25, stable disease in 2, and progressive disease in 0 with RECIST 1.1, and in 28, 2, 1, and 1, respectively, with PERCIST 1.0. For pCR prediction, the sensitivity, specificity, and accuracy with RECIST 1.1 were 28.6% (4/14), 94.4% (17/18), and 65.6% (21/32), and those with PERCIST 1.0 were 100% (14/14), 22.2% (4/18), and 56.3% (18/32). Five patients (15.6%) had recurrent development after a median period of 24 months (range 7.8–66.8 months). Patients who achieved CR shown by RECIST 1.1 showed slightly longer RFS than those who did not (p=0.46), whereas those with complete metabolic response (CMR) based on PERCIST 1.0 showed a relatively longer RFS than non-CMR patients (p=0.087). For prediction of pathological response to NAC in breast cancer, RECIST 1.1 and PERCIST 1.0 have complementary functions, however, FDG-PET as a post-NAC treatment assessment modality remains to be confirmed.