Tumor FDG Uptake Research Articles

Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer.

BackgroundDual inhibition of PI3K and MAPK signaling is conceptually a promising anticancer therapy.ObjectiveThis phase 1b trial investigated the safety, maximum tolerated dose (MTD), recommended phase II dose, pharmacokinetics, tumor response, fluorodeoxyglucose positron emission tomography (FDG-PET) pharmacodynamics, and biomarker explorations for the combination of pan-PI3K inhibitor copanlisib and allosteric MEK inhibitor refametinib in patients with advanced solid tumors.Patients and methodsThis was an adaptive trial with eight dose cohorts combining dose escalation and varying schedules in repeated 28-day cycles. Patients received copanlisib (0.2–0.8 mg/kg intravenously) intermittently (days 1, 8, 15) or weekly (days 1, 8, 15, 22) each cycle, and refametinib (30–50 mg twice daily orally) continuously or 4 days on/3 days off. Patients with KRAS, NRAS, BRAF, or PI3KCA mutations were eligible for the expansion cohort.ResultsIn the dose-escalation (n = 49) and expansion (n = 15) cohorts, the most common treatment-emergent adverse events included diarrhea (59.4%), nausea, acneiform rash, and fatigue (51.6% each). Dose-limiting toxicities included oral mucositis (n = 4), increased alanine aminotransferase/aspartate aminotransferase (n = 3), acneiform rash, hypertension (n = 2 each), and diarrhea (n = 1). MTD was copanlisib 0.4 mg/kg weekly and refametinib 30 mg twice daily. No pharmacokinetic interactions were identified. Decreased tumor FDG uptake and MEK-ERK signaling inhibition were demonstrated during treatment. Best response was stable disease (n = 21); median treatment duration was 6 weeks.ConclusionsDespite sound rationale and demonstrable pharmacodynamic tumor activity in relevant tumor populations, a dose and schedule could not be identified for this drug combination that were both tolerable and offered clear efficacy in the population assessed.Clinicaltrials.gov identifierNCT01392521.Electronic supplementary materialThe online version of this article (10.1007/s11523-020-00714-0) contains supplementary material, which is available to authorized users.

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

BackgroundAnti-programmed cell death 1 (PD-1) antibody is an immune checkpoint inhibitor, and anti-PD-1 therapy improves the anti-tumor functions of T cells and affects tumor microenvironment. We previously reported that anti-PD-1 treatment affected tumor glycolysis by using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET). That study showed that anti-PD-1 therapy in a mouse B16F10 melanoma model increased glucose metabolism in cancer cells at the point where anti-PD-1 therapy did not cause a significant inhibition of tumor growth. However, the B16F10 melanoma model is poorly immunogenic, so it is not clear how anti-PD-1 treatment affects glucose metabolism in highly immunogenic cancer models. In this study, we used a cyclic dinucleotide GMP-AMP (cGAMP)-injected B16F10 melanoma model to investigate the effect of anti-PD-1 therapy on [18F]FDG uptake in a highly immune activated tumor in mice.ResultsTo compare the cGAMP-injected B16F10 model with the B16F10 model, experiments were performed as described in our previous manuscript. [18F]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [18F]FDG uptake in tumors in the cGAMP/anti-PD-1 combination group was lower than that in the anti-PD-1 treatment group tumors on day 7, as shown by PET and ex vivo validation. Flow-cytometry was performed to assess immune cell populations and glucose metabolism. Anti-PD-1 and/or cGAMP treatment increased the infiltration level of immune cells into tumors. The cGAMP/anti-PD-1 combination group had significantly lower levels of GLUT1high cells/hexokinase IIhigh cells in CD45− cancer cells compared with tumors in the anti-PD-1 treated group. These results suggested that if immune responses in tumors are higher than a certain level, glucose uptake in cancer cells is reduced depending on that level. Such a change of glucose uptake might be caused by the difference in infiltration or activation level of immune cells between the anti-PD-1 treated group and the cGAMP/anti-PD-1 combination group.Conclusions[18F]FDG uptake in cancer cells after anti-PD-1 treatment might be affected by the tumor immune microenvironment including immune cell infiltration, composition, and activation status.

The Prognostic Value of Pretreatment FDG PET/CT in Patients with Oropharyngeal Squamous Cell Carcinoma

Traditional staging is developed with overall survival as sole endpoint. However, with more treatment options becoming available for patients with head and neck squamous cell carcinoma the risk of not only overall survival, but also the risk of local, regional and/or distant recurrence is relevant and important to aid in clinical decision making. Individualized treatment requires to address key questions: Whom to treat? Where to treat? As such, individualized treatment requires individualized prognostication beyond p16 status and UICC stage. The purpose of this study was to investigate if FDG uptake in primary tumor and lymph node metastases in patients with oropharyngeal squamous cell carcinoma (OPSCC) has a prognostic value beyond UICC8 staging and to develop a competing risk model with four clinically relevant endpoints.

GLUT1 expression in high-risk prostate cancer: Correlation with 18F-FDG-PET/CT and clinical outcome.

291 Background: Tumour FDG-uptake is of prognostic value in high-risk and metastatic prostate cancer (PCa). The aim of this study is to investigate the underlying glucose metabolism mechanisms of 18F-FDG-uptake on PET/CT imaging in PCa. Methods: Retrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 at biopsy who underwent 18F-FDG-PET/CT imaging before radical prostatectomy. GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on radical prostatectomy specimens by 3 pathologists. 18F-FDG-uptake in primary lesion was measured by a blinded reader using maximum standardized uptake value (SUVmax). Correlations between GLUT1, GLUT12 and HK2 and SUVmax were assessed using Spearman’s rank correlation test. Survival probabilities were based on the Kaplan-Meier method. Results: With a median follow-up of 4.5 years, 56% (n=53) of patients had biochemical recurrence, 7% (n=7) progressed to castration-resistant PCa (CRPC) disease, 13% (n=12) developed metastasis and 6% (n=6) died. Correlation was found between GLUT1 expression and SUVmax level (r=0.2512, p=0.0182). In addition, SUVmax was significantly higher in tumours with high GLUT1 expression (n=17, 5.74±1.67) than tumours with low GLUT1 expression (n=71, 2.68±0.31, P=0.0037). Also, contrary to GLUT12 and HEX2 expression, a significant association was found between GLUT-1 expression levels and SUVmax index (p=0.004), lymph node status (p=0.046), volume of cancer (P=0.013), CRPC-free survival (p=0.02) and metastasis-free survival (p=0.04). Conclusions: GLUT1 expression in PCa tumours correlates with 18F-FDG-uptake and poor prognostic factors. These results suggest that this transporter is involved in the molecular mechanism of 18F-FDG-uptake in high-risk PCa and raise interest in targeting metabolic dependencies of PCa cells as a selective anticancer strategy.

Abstract P2-16-22: Can we improve pCR prediction in early breast cancers treated with neoadjuvant chemotherapy using a simple machine learning algorithm based on 18-FDG and clinico-pathological parameters?

Abstract Purpose To test the hypothesis that a simple machine learning algorithm could improve pathological complete response (pCR) prediction in breast cancer patients treated with neoadjuvant chemotherapy (NAC) using an integrative approach based on clinico-pathological and metabolic factors. Methods A total of 311 patients with non-metastatic breast cancer were included. Baseline clinico-pathologic features were evaluated before NAC and tumor uptake of FDG was evaluated before and after one course of NAC. The predictive value of clinico-pathologic and metabolic parameters on pCR was calculated by means of logistic regression analysis and a simple machine learning algorithm generating a hierarchical predictive model using a classification and regression tree (CART). Results: The CART model performed better than all the clinico-pathological and metabolic parameters that were predictive of pCR after univariate analysis. The CART model identified five different groups (G): G1 (luminal cancer with Ki67≤30%), G2 (luminal cancer with Ki67>30% and baseline SUVmax≤10.1), G3 (luminal cancer with Ki67<30% and baseline SUVmax> 10.1), G4 (Her2 positive or triple negative cancer with ΔSUVmax ≤50%) and G5 (Her2 positive or triple negative cancer with ΔSUVmax >50%). The pCR rates predicted by the model for each of the identified groups were G1: 7.2%, G2: 16.7%, G3: 54.6%, G4: 35% and G5: 85% Conclusion This study showed that CART, a simple machine learning algorithm, integrating clinico-pathological and metabolic parameters easily obtainable in routine clinical practice, can improve pCR prediction in early breast cancer and identify subgroups that will not benefit from NAC Baseline patient characteristics of the entire cohort and according to the tumor subtypeCharacteristicsGlobalLumALumBHER2THN311321198476Age (median)4950.249.351.143.3Histological type NST/Other290/2127/5107/1281/375/1Grade 14%22%4%1%0%Grade 237%56%46%32%19%Grade 357%22%47%62%80%Grade missing2%0%3%5%1%ER+58%100%89%45%0%PgR+48%88%75%37%0%ER and PgR neg36%0%0%43%0%HER2 positif27%0%0%100%0%Nodal status negative32%13%32%35%33%Nodal status positive64%50%63%63%61%Nodal status missing data4%37%5%2%6%Stage 11%0%0%0%1%Stage 2A25%28%24%11%28%Stage 2B26%34%24%31%17%Stage 3A16%9%17%13%18%Stage 3B21%22%23%25%17%Stage 3C7%3%7%5%11%Missing stage5%3%5%4%8%mean SUV max (PET-FDG)8.94.859.28.411.7 Univariate and multivariate analyses for pCR predictionVariablepCR (%)OR (95% CI)Univariate analysisp valueOR (95% CI)Multivariate analysisp valueMolecular subtypeLum A1 (3.1)0.15 (0.01-0.076)<0.0010.44 (0.02-2.71)0.029Lum B22 (17.7)11HER241 (48.8)4.42 (2.38-8.41)3.64 (1.40-9.65)TN31 (43.7)3.59 (1.87-7.01)1.65 (0.56-5.02)Histiological grade1/224 (18;8)1<0.001368 (38.6)2.73 (1.61-4.74)Baseline Ki67<=30%26 (19)1<0.001>30%60 (41.4)3.01 (1.77-5.23)AJCC TNM Stage0.36nodal statusN033 (33)0.53N+58 (29)Body surface area<=1.73160 (52.8)2.11 (1.28-3.51)0.003>1.73143 (47.2)1Baseline SUV max<=10.127 (22)1<0.00110.04>10.139 (47.6)3.22 (1.77-5.98)2.24 (1.04-4.67)Delta SUV max<50%17 (22.7)1<0.001>=50%22 (66.7)6.82 (2.83-17.41) Citation Format: Marc-Antoine Benderra, Martine Antoine, Sonia Zilberman, Sandrine Richard, Fatima Kebir, Sofiane Bendifallah, Jean-Pierre Lotz, Emile Darai, Joseph Gligorov, Khaldoun Kerrou. Can we improve pCR prediction in early breast cancers treated with neoadjuvant chemotherapy using a simple machine learning algorithm based on 18-FDG and clinico-pathological parameters? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-22.

Can PET-CT predict diagnostic success in ultrasonography-guided transthoracic fine needle aspiration biopsies in lung cancers?

ObjectiveTo examine any correlations between tumor maximum standard uptake values (SUVmax) in positron emission tomography-computed tomography (PET-CT) and homogeneous/heterogeneous tumor FDG uptake in PET-CT, and the diagnostic success of the procedure in thoracic ultrasonography (US)-guided transthoracic fine needle aspiration biopsy (TFNAB). MethodsThe files of patients who underwent thoracic US-guided TFNAB between 2013 and 2018 were examined. Patients who underwent thoracic US-guided TFNAB and were diagnosed as having primary lung cancer were considered as the US-TFNAB diagnostic group. Patients whose disease was diagnosed as primary lung cancer using a different diagnostic method (e.g. CT-guided biopsies, fiberoptic bronchoscopy) due to a lack of diagnosis despite undergoing thoracic US-guided TFNAB were allocated to the US-TFNAB non-diagnostic group. The clinical and radiologic characteristics and PET-CT parameters of the two groups were compared. ResultsA total of 104 patients were included in the study; 79 (76%) patients whose disease was diagnosed using US-guided TFNAB, and 25 (24%) patients whose primary lung cancer could not be diagnosed with US-guided TFNAB. The mean SUVmax value of the US-TFNAB diagnostic group was 19.5 ± 10.1, whereas it was 15.1 ± 8.9 in the US-TFNAB non-diagnostic group (p = 0.016). Whether a lesion showed homogeneous or heterogeneous FDG uptake did not effect diagnostic success (p = 0.289). SUVmax value was the only effective independent factor in the diagnostic success of the procedure (p = 0.035). ConclusionsHigh SUVmax values in PET-CT in lung cancers may increase the diagnostic success of US guided-TFNAB procedures.

Axillary Staging with Supine 18F-FDG PET/CT Is Useful In Breast Cancer Patients Undergoing Tailored Axillary Treatment after Neoadjuvant Systemic Treatment According to the MARI Protocol

Background: Staging for distant and regional disease in breast cancer patients before start of neoadjuvant systemic therapy (NST) can be performed with 18F-FDG PET/CT in supine position. To tailor axillary treatment after NST, FDG-PET/CT is combined with the MARI procedure (Marking Axillary lymph nodes with Radioactive Iodine seeds) at the Netherlands Cancer Institute (NCI). In patients with ≥4 FDG positive axillary lymph nodes (ALNs) on FDG-PET/CT pre-NST and a tumor-positive MARI node post-NST an axillary dissection (ALND) is performed, whereas a negative MARI node is followed by axillary radiotherapy. To improve visualization of FDG-uptake in the primary tumor, a prone position scan protocol is used in addition to a supine FDG-PET/CT. The aim of this study is to assess the value of this prone position FDG-PET/CT in addition to the supine FDG-PET/CT for axillary staging.

The role of PET/CT in determining egfr mutation and ALK rearrangement in patients with lung adenocarcinoma

Aim: The aim of the present study is to evaluate the role of tumor FDG uptake in a non-invasive method and the use of positron emission tomography / computed tomography (PET/CT) in estimating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in cases of adenocarcinoma of the lung.Material and Methods: A total of 115 patients with the diagnosis of an adenocarcinoma of the lung that underwent F-18 FDG PET/CT for staging and whose EGFR mutation and ALK rearrangement status were analyzed were retrospectively analyzed. The association of the PET parameters (SUVmax, SUVmean, MTV and TLG) of primary tumor with the molecular profile was analyzed.Results: EGFR mutations (EGFR+ group) and ALK rearrangements (ALK+ group) were found in 15 (13%) and 10 (8.7%) of 115 patients; and 90 patients (78.3%) had no EGFR mutation or ALK rearrangement (EGFR/ALK-). EGFR mutations were found to be significantly higher among the never-smoked group (p=0.009). No significant association was identified between the SUVmean, MTV and TLG values and EGFR mutations; however, patients with a low SUVmax value were found to have a significantly higher rate of EGFR mutation (p=0.034). No statistically significant differences were found between the ALK+ and ALK- group in terms of age, sex, cigarette smoking status, tumor stage, or PET parameters.Conclusion: Our study results suggest that a low SUVmax value in lung adenocarcinomas is associated with EGFR mutation, although the diagnostic efficacy is not high.

High nodal FDG uptake increases risk of distant metastasis in patients with oropharyngeal squamous cell carcinoma.

The purpose of this study was to investigate if FDG uptake metrics in primary tumor and lymph node metastases in patients with oropharyngeal squamous cell carcinoma (OPSCC) has a prognostic value beyond UICC8 staging in a multiple endpoint model. Patients with OPSCC treated with primary radiotherapy at Rigshospitalet in the period 2010-2017 were included. All patients had a pretreatment FDG PET/CT scan performed. Four cause-specific Cox regression models were built for the hazard ratios (HR) of recurrence in T-, N-, M-site, and death with no evidence of disease (NED), respectively. The following variables were included: T-, N-stage, p16 status, metabolic tumor volume, and FDG uptake in both primary tumor and lymph nodes. A competing risk analysis was performed and absolute risk estimates were estimated using the Aalen-Johansen method. Overall, 441 patients were included. Thirty-four patients had T-site recurrence, 31 N-site recurrence, 32 M-site recurrence, and 52 patients had death NED as event. Nodal FDG uptake had a significant impact on N- and M-site recurrence, with HRs of 2.13 (CI 1.20-3.77) and 2.18 (CI 1.16-4.10). The individual prognostication of absolute risk of the four events for any given patient can be assessed in the online tool (https://rasmussen.shinyapps.io/OPSCCmodelFDG_PET/). High nodal FDG uptake increases the risk of N- and M-site recurrence in patients with OPSCC in a competing risk scenario. The reported results are available in an easy applicable online tool and can help identify relevant candidates for future trials testing treatment approaches.

Utilization of18F-Fluorodeoxyglucose–Positron Emission Tomography To Understand the Mechanism of Nicotinamide Phosphoribosyltransferase Inhibitors In Vivo

Cancer cells are highly dependent on NAD+/NADH produced via the nicotinamide salvage pathway. The rate-limiting enzyme in this pathway is the nicotinamide phosphoribosyltransferase (NAMPT), which we have targeted with novel NAMPT inhibitors. NAMPT inhibition elicits depletion of total cellular NAD+ levels and ultimately cytotoxicity via depletion of cellular ATP levels. 18F-fluorodeoxyglucose- positron emission tomography (FDG-PET) is a translational imaging tool to assess glucose utilization in tumors and normal tissue. We used FDG-PET to understand the timing of ATP depletion in vivo and better understand the pharmacology of NAMPT inhibitors. Because of the intimate relationship between cellular ATP levels and cell viability, we developed an in-depth understanding of our NAMPT inhibitor pharmacology and the relationship with changes in tumor FDG uptake. Taken together, we show that FDG-PET could be used as a biomarker in clinical studies to understand dose and provide proof of mechanism for NAMPT inhibitors. SIGNIFICANCE STATEMENT: Our imaging data suggest that tumor 18F-fluorodeoxyglucose uptake can provide insight into the ATP status inside the tumor after nicotinamide phosphoribosyltransferase (NAMPT) therapy, with a novel NAMPT inhibitor. Such an approach could be used clinically as a pharmacodynamic biomarker to help understand the implications of dose, schedule, rescue strategy, or other clinical biomarkers.

FDG PET/CT of Mediastinal Epithelioid Hemangioendothelioma

Epithelioid hemangioendothelioma is a rare low- to intermediate-grade malignant vascular neoplasm with a variable clinical course and currently no standardized treatment. We present a case of a 65-year-old woman diagnosed as having mediastinal epithelioid hemangioendothelioma, a location which is very exceptional. FDG PET/CT was more sensitive than CT for staging, revealing intense FDG uptake in the primary tumor and in the metastatic disease. Despite high FDG uptake, the disease was stable with no further specific treatment. Only few reports utilizing FDG PET/CT are available; review of the literature on this subject is included.

Pilot study to enhance FDG-PET imaging of prostate cancers with the metabolic inhibitor ranolazine.

e16551 Background: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) is a widely-used imaging modality for many cancers; however, its utility in prostate cancer is limited. Fatty acid oxidation (FAO) is a primary source of energy for early prostate cancer. We previously demonstrated that FAO inhibition in prostate cancer mouse models resulted in increased glucose metabolism and enhanced tumor FDG uptake, with peak uptake at 24 hours. To validate these preclinical findings, we conducted a pilot study to evaluate whether a partial FAO inhibitor, ranolazine, increases tumor FDG uptake on PET imaging for prostate cancer. Methods: Prostate cancer patients with untreated localized cancer (arm 1) and with metastatic disease on hormonal or other therapy (arm 2) were enrolled and underwent baseline and post-treatment FDG-PET/CT scans (standard dose of 10 mCi FDG). Ranolazine 1000mg PO BID x 2 doses was given within 24-48 hours of the second scan. The primary objective was to evaluate the rate of successful enhancement of FDG uptake on PET imaging, based on one or more of the following criteria: 30% increase in maximum SUV with an absolute change of 2 units; 30% increase in mean SUV with an absolute change of 0.75 units; or 20% increase in mean SUV with an absolute change of 1 unit. Results: Eleven patients (four in arm 1, seven in arm 2) were enrolled. Ranolazine was well tolerated by all participants, with no adverse effects observed. Both increases and decreases in SUV uptake were observed on the post-ranolazine scans. No patient met the predefined criteria for successful enhancement of FDG uptake. There was an incidental finding of thyroid cancer seen in one patient that was discovered on PET imaging. The study was closed early due to the emerging clinical availability of alternative and effective PET imaging modalities such as [11C] choline, [18F] fluciclovine, [68Ga] PSMA, and [18F] sodium fluoride. Conclusions: Given the small sample size, we were not able to make any firm conclusions. In this limited study, ranolazine treatment did not result in enhanced FDG-PET-tumor detection. ClinicalTrials.gov identifier: NCT01992016. Supported by the William Meyn Foundation; NIH/NCI P30CA46934, 5K12CA086913, CA168934; ACS RSG-16-256-01-TBE; Colorado Translational Research Imaging Center Pilot Award; Paul Sandoval Cancer Research Summer Fellowship. Clinical trial information: NCT01992016.

PET-directed combined modality therapy for gastroesophageal junction cancer: First results of the prospective MEMORI trial.

4018 Background: We evaluated a PET-guided treatment stratification for improvement in obtaining negative surgical margins (R0) in resectable gastroesophageal junction (GEJ) adenocarcinoma. According to sequential 18F-FDG PET, only 40–50% of patients (pts) respond to neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in this interventional, prospective, non-randomized multicenter trial. Pts underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (physicians’ choice, e.g. EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders (P-R), defined as ≥ 35% decrease in SUVmax from baseline, continued with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly carboplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT. Primary objective was an improvement of R0 resection rates in P-NR above a proportion of 70% based on results from the MUNICON1/2 trials. Secondary endpoints include disease-free survival (DFS), overall survival (OS), measured from randomization to death from any cause, and translational endpoints. Results: Between 12/2014 and 07/ 2018 160 pts with resectable GEJ adenocarcinomas were prospectively screened with PET in three German university centers. Overall, 85 pts (53%) could not be included due to previously undetectable metastases (40/25%), no or too low FDG uptake of the primary tumor (21/13%), other reasons (24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable. Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respectively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for P-NR. Pathologic complete remission (pCR; < 10% vital tumor cells), was 33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75% for P-NR. Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0- and pCR rates among pts who were P-NR after induction CTX. PET response was prognostic for a prolonged OS and DFS. Clinical trial information: 2014-000860-16.

Visceral adipose tissue volume and CT-attenuation as prognostic factors in patients with head and neck cancer.

The aim of this study was to evaluate the relationship of the characteristics of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) to the disease progression-free survival and distant failure-free survival of head and neck squamous cell carcinoma (HNSCC). We enrolled 152 HNSCC patients who underwent staging 18 F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT). Maximum FDG uptake (standardized uptake value [SUV]) and total lesion glycolysis (TLG) of the primary tumor and volume, CT-attenuation (Hounsfield units [HU]), and FDG uptake of SAT and VAT were measured. Survival analysis using Cox proportional hazard modeling was performed to assess the relationship between the adipose tissue parameters of PET/CT and survival. Patients with low VAT volume and high VAT HU had significantly worse progression-free survival and distant failure-free survival than those with high VAT volume and low VAT HU. On multivariate analysis, the volume and HU of VAT were significantly correlated with disease progression-free survival and distant failure-free survival after adjusting for age, sex, body mass index, TNM stage, serum C-reactive protein, maximum SUV, and TLG. The volume and CT-attenuation of VAT were significantly correlated with disease progression-free survival and distant failure-free survival in patients with HNSCC.

Relationship between primary tumor FDG uptake and extensional or metastatic potential in patients with small cell lung cancer

Abstract Objective: To explore the maximum standardized uptake vаlue (SUVmаx) of primаry tumors, аs well аs the relаtionship between SUVmаx with tumor size, with tumor

Non‑invasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDG‑PET/CT and CT.

We established patient‑like models of lung cancer metastasis by orthotopically implanting human non‑small cell lung cancer cell lines into SCID mice. We evaluated the utilities of small‑animal computed tomography (CT) and positron‑emission tomography‑computed tomography (PET/CT) in these models to non‑invasively and repeatedly monitor the anticancer effects of cisplatin and erlotinib. We orthotopically implanted three non‑small cell lung cancer cell lines, A549, FT821 and PC‑9, into SCID mice. These mice were then divided into three groups: Control, cis‑diamminedichloroplatinum(II) (CDDP) (7‑mg/kg CDDP, single administration intraperitoneally), and erlotinib (25mg/kg erlotinib/day, oral administration 5days/week). After treatment initiation, we repeatedly performed PET/CT and CT measurements and assessed anticancer effects based on tumor volumes and FDG uptake. A549 tumors were not affected by CDDP or erlotinib. FT821 tumors were highly responsive to CDDP. PC‑9 tumors, which have an epidermal growth factor receptor mutation, were highly responsive to erlotinib. Histological results and metastatic rates correlated with the anticancer effects shown by CT. In our orthotopic SCID mouse lung cancer models, 18FDG‑PET/CT and CT imaging non‑invasively and repeatedly monitored the efficacies of cisplatin and erlotinib against not only implanted tumors, but also mediastinal lymph node metastases.

The Prognostic Value of 18F-FDG PET/CT in Monitoring Chemotherapy in Ovarian Cancer Both at Initial Diagnosis and at Recurrent Disease

Published experiences related to the prognostic relevance of negative or positive FDG PET/CT in patients treated for ovarian cancer for progression-free survival and overall survival are typically heterogeneous retrospective analyses. Several points have been well defined, these are as follows: (a) there is a correlation between FDG tumor uptake and prognosis; (b) ovarian cancer patients treated by neoadjuvant or adjuvant chemotherapy can be divided into responders with reduction in tumor FDG uptake during and after treatment and nonresponders where tumor FDG uptake remains stable or increases after treatment;

PS02.075: USEFULNESS OF FDG-PET TO DECIDE THE INDICATION FOR ENDOSCOPIC RESECTION FOR SUPERFICIAL ESOPHAGEAL CANCER

Abstract Background 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful imaging modality to reflect the tumor activity. However, FDG-PET is mainly used for advanced cancer rather than superficial cancer. In this study, we investigate the relationship between the superficial tumor depth of esophageal cancer and FDG uptake, and discuss the possibility of using FDG-PET in making the decision for performing endoscopic resection. Methods From 2009 to 2017, 444 esophageal cancer patients underwent esophagectomy or Endoscopic submucosal dissection (ESD), and 195 were diagnosed with pathological superficial cancer. Among them, 146 patients were examined by FDG-PET before esophagectomy or ESD. For these 146 patients, the relationship between pathological tumor depth and FDG uptake was analyzed. Results Mean maximun standardized uptake value (SUV Max) in pT1a-EP/LPM was 1.362 ± 0.890, pT1a-MM/pT1b-SM1 was 2.453 ± 1.872, and pT1b-SM2/SM3 was 4.265 ± 3.233 (P < 0.0001). Among 51 pT1a-EP/LPM tumors, 10 (19.6%) showed positive detection of FDG. For pT1a-MM/pT1b-SM1 and pT1b-SM2/SM3, the detection rates were 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate for pT1a-EP/LPM was significantly lower than for the other two groups (P < 0.0001). Among 10 FDG-PET positive patients, the reason for one lesionbeing PET positive could not be determined; however, nine of ten lesions had suitable reasons for the lesions being detected by PET and thus not being ER indication. PET diagnosis tends to be more accurate than endoscopic diagnosis (P = 0.0574) Conclusion Negative detection of superficial esophageal sqamous cell carcinoma by FGD-PET is useful for deciding the indication for ER. Furthermore, when FDG uptake is recognized, a therapeutic modality other than ER should be considered. Disclosure All authors have declared no conflicts of interest.

Correlation of 18F-FDG uptake and thyroid cancer stem cells.

2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) has the potential to detect various types of cancers, including thyroid cancer (TC), at a potentially curable stage. Increased uptake of 18F-FDG was observed in anaplastic and poorly differentiated thyroid cancer cells, and PET-positive tumors are more likely to be resistant to 131I treatment. As cancer stem cells (CSCs) possess a dedifferentiated phenotype and are resistant to many anticancer therapies, we hypothesized that the expression of CSC-related markers is correlated with the ability of tumor cells in TC to uptake FDG. The present study cohort included 12 patients with TC, who underwent 18F-FDG PET/CT imaging before surgery. Quantitative polymerase chain reaction (QPCR) and immunohistochemical (IHC) staining were performed to analyze the expression patterns of gene markers related to embryonic stem (ES) cells and CSCs in TC. The mRNA expression levels of CSC- (CD133 and CD44) and ES-related genes (Oct4 and Nanog) were higher in TC tissue than in normal thyroid tissue, whereas the mRNA expression levels of thyroid-specific genes (Tg, TSHR, and TTF1) were higher in normal thyroid tissue than in TC tissue. There was a positive and statistically significant correlation between FDG uptake (SUV<inf>max</inf>) of tumor and relative mRNA levels of CD133, CD44, Oct4, and Nanog. The IHC results demonstrated that CD133 and Nanog were expressed in TC tissue but not in normal thyroid tissue, however, CD44 expression was observed in both TC and normal thyroid tissue. Comparisons of the clinicopathological parameters between TC tissues with low and high SUV<inf>max</inf> demonstrated significant differences in protein level of CD133 but not in that of Nanog. The pre-therapeutic tumor SUV<inf>max</inf> obtained from 18F-FDG PET/CT may be a potential predictor for evaluating the proportion of CSC population in individual patients with TC.

Anti\xa0PD-1 treatment increases [18F]FDG uptake by cancer cells in a mouse B16F10 melanoma model

BackgroundProgrammed cell death 1 (PD-1) inhibitors act as immune checkpoint inhibitors and are more effective for improving survival time with less toxicity as compared with conventional chemotherapies. In anti PD-1 therapy, it is important to evaluate metabolism in the cancer microenvironment, as this helps to clarify the pathological conditions. Herein, we investigate the early effects of PD-1 therapy on 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells.ResultsIn a B16F10 melanoma model, [18F]FDG-positron emission tomography (PET) was performed before treatment and 7 days after the start of treatment. Values were calculated as the percentage-injected activity per gram of tissue (%IA/g). Flow-cytometry was then performed to assess immune cell populations and glucose metabolism. There was a negligible difference in [18F]FDG uptake between tumors in the treatment group and non-treatment group before the treatment. In contrast, mean [18F]FDG uptake in the treatment group tumors was significantly higher (8.06 ± 0.48 %IA/g; P = 0.0074) than that in the non-treatment group (4.02 ± 1.03 %IA/g) after anti PD-1 treatment. Assessment of tumor immune cell populations showed that treatment slightly enriched CD8+ T cells and CD4+ T cells; however, infiltration of immune cells was negligible, and thus, immune cells were not responsible for the increase in [18F]FDG uptake. On the other hand, anti PD-1 treatment significantly increased glucose transporter 1 (GLUT1) and hexokinase II expression in CD45− cancer cells, indicating that anti PD-1 treatment increased glucose metabolism in cancer cells.ConclusionThe present study shows that anti PD-1 therapy increases glucose metabolism in cancer cells.