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Abstract Background Two-deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (PET) is useful for detecting malignant lesions; however, the clinical significance of cardiac 18F-FDG uptake in patients with cancer remains unclear. This preliminary study explored the relationship between cardiac 18F-FDG uptake and advanced diseases such as cancer cachexia in non-small cell lung cancer (NSCLC). Methods Forty-three patients with advanced NSCLC who underwent 18F-FDG PET and complained of weight loss before the first-line systemic therapy were retrospectively included in this study. Visual assessment using a 5-point scale based on 18F-FDG uptake was performed; a cut-off score of 3 was determined, a low score was 1, 2, or 3, and a high score was 4 or 5). Results High and low visual cardiac 18F-FDG uptakes were observed in 27 (62.8%) and 16 (37.2%) patients, respectively. Of the 43 patients, 17 (39.5%) definitely had cachexia, and 26 (60.5%) did not. A low visual score and standardized uptake valuemax for cardiac 18F-FDG uptake were significantly associated with high metabolic tumor activity (p = 0.009, and p = 0.009, respectively) and a high neutrophil-to-lymphocyte ratio (p = 0.016, and p = 0.047, respectively), whereas a low visual score for cardiac 18F-FDG uptake and high metabolic tumor activity were significantly associated with cachexia (p = 0.004). The amount of cardiac 18F-FDG accumulation depicted a close relationship with body mass index, low weight loss, and inflammation. The combination of cachexia and low visual cardiac 18F-FDG uptake was identified as a significant predictor for poor overall survival (OS) (p = 0.034). Conclusion Decreased visual cardiac 18F-FDG uptake was associated with poor nutritional status and OS, and cachexia in patients with advanced NSCLC.

Abstract Purpose To 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). Methods A 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. Results The 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. Conclusions The 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.

Abstract Anti-programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies are administered in varied human cancer types. The expression of PD-L1 within tumor cells has been identified as a predictive marker, although assessing its expression has benefitted only patients with non-small cell lung cancer (NSCLC) or head and neck cancer. Whereas, more than 75% of the patients with NSCLC showing partial response to PD-1 blockade therapy experienced long-term survival for more than 5-years Thus, identifying the responders to PD-1 blockade at early phase after its initiation is of clinical importance. The 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) on positron emission tomography (PET) can evaluate any tumor shrinkage by assessing the metabolic tumor volume at an earlier phase than conventional modalities such as computed tomography (CT). While several reports describe the correlation of PD-L1 expression with 18F-FDG uptake rate in the tumor cells, it remains to be delineated whether this rate determined by the glucose metabolism and hypoxia is associated with the status of immune microenvironment, including the expression of PD-L1. Moreover, details of the relationship between expression of PD-L1 and 18F-FDG uptake is still unclear. Therefore, we reviewed the clinical significance of 18F-FDG uptake on PET as a predictor of the efficacy of PD-1 blockade therapy, by correlating with the expression of PD-L1, in patients with several neoplasms.

Abstract Background Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of 18F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer. Methods Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with 18F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR. Results Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-α, and interleukin 8. Conclusions FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status. Trial registration UMIN Clinical Trials Registry, UMIN000006802. Registered on 1 December 2011.

After the publication of this article [1], we noticed that in Fig. 2, the survival curve images (C and D, lower panel) were incorrect. The corrected Fig. 2 is presented below. The correction does not affect in any our results and conclusions.