Serial 18F-FDG Research Articles

Using serial 18F-FDG PET/CT PERCIST response to predict responses to immune check point inhibitors in patients with advanced cutaneous squamous cell carcinoma.

9548 Background: The role of serial 18F-FDG-PET/CT imaging in predicting long term efficacy of PD-1 targeted immune checkpoint inhibitor (ICI) in advanced cutaneous squamous cell carcinoma (cSCC) is unknown. This study aims to correlate PET PERCIST response with time to progressive disease. Methods: This was a single-centre retrospective study of patients treated with ICI for advanced cSCC who had baseline and serial FDG-PET/CT within 4-months of commencement of ICI. PERCST 1.0 was calculated by two radiologists independently and classified into complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). The primary endpoint was time to progression from commencement of ICI. Progression was determined by a multidisciplinary team combining clinical and radiological assessments. Results: Of the 242 patients treated with ICI for advanced cSCC during 2018-2023, 83 (34%) patients had a serial FDG PET. Of these, 53 patients met the inclusion criteria of ≤4-months from ICI to second PET. CMR (54.7%), PMR (15.1%), SMD (11.3%) and PMD (18.9%) were seen as initial responses by PERCST 1.0. With a median follow-up of 8-months (1-55), progressive disease as determined by the multidisciplinary team was observed in 11 patients (21%). For these 11 patients, the 4-month PERCST 1.0 response was measured as CMR (n=1), PMR (N=1), SMD (N=2) and PMD (N=7). The median TTP was significantly higher in CMR/ PMR vs SMD/PMD (55 vs 4-Months, P<0.001). At data cut off, 94.6% (N=35) of patients with a 4-month PET PERCST 1.0 CMR/ PMR assessment did not progress clinically. Clinical response was maintained at a minimum of 12-months in 94.7% (n=18) of those responding. Conclusions: Rate of CMR and PMR in advanced cSCC is high with ICI. Early PET CMR/ PMR appears to predict long term durable responses. Incorporation of PET/CT into the assessment of response in cSCC may help guide treatment decisions by early identification of those patients not responding to ICI.

Prospective pilot study utilizing changes in quantitative values obtained on serial fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in dogs with appendicular osteosarcoma before and after stereotactic body radiation therapy (SBRT) and carboplatin chemotherapy to assess for prediction of survival and therapeutic effectiveness.

Serial fluorine 18 fluorodeoxyglucose (18F-FDG) positron emission tomography-CT (PET/CT) is commonly used in human oncology to prognosticate and evaluate for therapeutic effectiveness. In this pilot study, dogs with naturally occurring appendicular osteosarcoma were evaluated with serial 18F-FDG PET/CT in an attempt to assess for response to therapy, prognostic factors, and appropriateness of imaging intervals. Fourteen dogs were enrolled in the trial. All dogs had the initial 18F-FDG PET/CT (PET1), with nine dogs having their end-of-therapy 18F-FDG PET/CT (EoT PET) 3 months after stereotactic body radiation therapy (SBRT) to the primary tumor. The median percent change from the PET1 to the EoT PET for the standard uptake value maximum (SUVmax%) was -58% (range: -17 to -88%), metabolic tumor volume (MTV%) was -99.8% (range: -65 to -100%), and total lesion glycolysis (TLG%) was -99.8% (range: -75 to -100%), all of which were significant (P<.05, <.05, and <.05, respectively). On evaluation, it was found that volumes of GTV and CTV were significant for survival (P<.05 and <.05), MTV1, TLG1, and SUVmax on the EoT PET (SUVmaxEoT) were predictive of metastasis (P<.05), and the SUVmax% was significantly correlated to the time to first event (P<.05). Based on this data, serial 18F-FDG PET/CT performed 3 months after SBRT can show a significant reduction in avidity, and the quantitative data collected may help predict metastatic disease in canine appendicular osteosarcoma.

Targeting CXCR4/CXCL12 axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 with CXCR4 antagonist in triple-negative breast cancer

PurposeRadiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC).MethodsPublic database was first interrogated to reveal the correlation between CAFs’ scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen.ResultsCAFs’ scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12.ConclusionThe combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.

Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials

BackgroundStandard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.MethodsFor this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment.ResultsThe mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak.ConclusionIn evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.

Chronic physical exercise alleviates stress-associated amygdala metabolic activity in obese women: A prospective serial 18F-FDG PET/CT study.

Psychological stress is considered as a major risk factor for cardiovascular disease (CVD). Chronic exercise is known to reduce CVD risk partly through attenuating psychological stress. Obesity has been linked with increased levels of psychological stress. We aimed to prospectively evaluate whether physical exercise could alleviate stress-associated amygdala metabolic activity, assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in women with obesity. A total of 43 participants were enrolled in this study. Twenty-three obese women were participated in a physical exercise program 5 days per week for 3 months. The exercise program consisted of aerobic exercise and resistance training. Serial 18F-FDG PET/CT was taken before the start of physical exercise program (baseline) and after finishing the program (post-exercise). A total of 20 participants who underwent 18F-FDG PET/CT for general health check-up were enrolled as non-obese control group. Brain amygdala activity (AmygA) was calculated as maximum standardized uptake value (SUVmax) of amygdala normalized to mean SUV of temporal lobe. Chronic physical exercise significantly reduced AmygA and improved body adiposity and systemic inflammation. AmygA was highest in baseline, intermediate in post-exercise, and lowest in non-obese control group (0.76 ± 0.17, 0.61 ± 0.1, 0.52 ± 0.09, p < 0.001). Furthermore, physical exercise also abrogated the association of AmygA with systemic inflammation. Chronic physical exercise reduced stress-associated amygdala metabolic activity and broke its association with systemic inflammation in obese women. This study could explain the putative mechanism underlying the health beneficial effect of exercise on CVD via attenuation of stress neurobiology.

Process of Hard Palate Osteonecrosis Demonstrated on Serial 18F-FDG PET/CT Scans.

Osteonecrosis of the hard palate is rare. Here, we demonstrated the dynamic metabolic and structural changes during the process of osteonecrosis of the hard palate by serial 18F-FDG PET/CT scans in a patient with nasal NK/T-cell lymphoma. On the baseline scan, increased FDG uptake in the periphery of the hard palate could be observed. On the following scans after treatment, a focal metabolic defect on the hard palate with no structural changes and with bone sequestration and perforation have been observed successively. Our case indicates that the metabolic defect on 18F-FDG PET/CT may be an early sign of osteonecrosis.

Pathological complete response with immunotherapy and brachytherapy to 15 metastatic liver lesions in a single patient.

Materials & methods:High dose rate interstitial brachytherapy (HDR-IBT) treatment plan for 15 metastatic liver lesions in a patient with pancreatic cancer was retrieved and analyzed for liver dose parameters and diaphragm dose. Serial 18F-FDG PET-CT scans were reviewed for disease response assessment and left liver lobe volume. Serial laboratory records were analyzed for liver parameters.Results:Left liver lobe volume increased from 241 cm3 pre-HDR-IBT to estimated 600 cm3 after seven sessions of HDR-IBT. Metabolic complete response (CR) and subsequently pathological CR was confirmed in the right hepatotectomy specimen for all the 15 PET-CT avid lesions treated with HDR-IBT. Maximum diaphragm dose in a single fraction was 82 Gy. The liver parameters were stable and patient did not develop radiation induced liver disease.Discussion:This is the largest reported series of HDR-IBT to liver lesions in a single patient. This first ever reported combined treatment of immunotherapy (IT) and HDR-IBT had likely rendered this patient disease free both at local the liver and systemically. Metabolic CR by PET-CT can be seen as early as 46 days after HDR-IBT. Diaphragm can tolerate very high doses of radiation and repeated treatment.Conclusion:In this patient HDR-IBT for multiple liver lesions with IT is well tolerated. PET-CT can be used for response assessment of HDR-IBT liver. Synergistic effect of IT with HDR-IBT and it’s role as bridging for liver resection has clinical potential and should be further studied in prospective trials.

Patients undergoing multiple 18F-FDG PET/CT exams: Assessment of frequency, dose and disease classification.

To analyse the frequency, demographics, primary disease and cumulative effective dose of patients undergoing two or more 18F-FDG PET/CT examinations in a year. In a retrospective study performed at a tertiary-care hospital, patients who underwent ≥2 18F-FDG PET/CT scans in a calendar year were identified for two consecutive years. The CT radiation dose was calculated using dose-length-product and sex-specific conversion factors. The primary malignancy of patients was retrieved from electronic medical records. 10,714 18F-FDG PET/CT exams were performed for 6,831 unique patients in 2 years, yielding an average of 1.6 exams per patient. The maximum number of 18F-FDG PET/CT examinations any patient underwent in a single year was seven. 20.9% patients had ≥2 18F-FDG PET/CT exams in any single year. Thirty nine percent patients in the cohort were below 60 years age. The median dose for 18F-FDG PET/CT examination was 25.1 mSv and maximum value reaching 1.7 to 2.9 times the median value. Cumulative effective dose (CED) was≥100 mSv in 12-13% of the patients. The cumulative dose for both years combined demonstrated the 25th percentile, 50th percentile and 75th percentile as well as the mean to be over 100 mSv, with the 25th percentile being 109 mSv. The dominant primary malignancies contributing to serial 18F-FDG PET/CTs in decreasing frequency were melanoma, non-Hodgkin's lymphoma (NHL), gastrointestinal cancer, breast cancer and Hodgkin's lymphoma. A sizeable number of patients undergo≥2 18F-FDG PET/CT exams with one out of every eight patients receiving cumulative dose≥100 mSv and that includes patients with long-life expectancy. The study found that one of five patients had≥2 18F-FDG PET/CT exams in a calendar year, one of four patients in two years and one of eight patients received cumulative dose≥100 mSv. Top malignancies associated with serial imaging in decreasing order of frequency included melanoma, non-Hodgkin's lymphoma (NHL), gastrointestinal cancer, breast cancer and Hodgkin's lymphoma.

Long-term control of melanoma adrenal metastasis treated with radiotherapy.

Melanoma remains a large global burden with a significant proportion of patients succumbing to metastatic disease. The adrenal gland is a common area for metastasis with surgical treatment as the main modality. Radiotherapy is less utilised in this setting with uncertainty over deliverability and efficacy. Here, we present the details and outcomes of 20 patients treated with radiotherapy, with or without systemic therapy, for melanoma adrenal metastasis in a single institute. Twenty patients were identified from radiation treatment and medical records from between 2015 and 2019 at our institution. Three patients had bilateral radiotherapy treatments and therefore 23 adrenal lesions were analysed. Demographics, indications for treatment, radiotherapy methodology and outcomes were recorded. Outcomes were based on serial 18F FDG PET/computerized tomography scans reporting using the PERCIST criteria. The most common indication for radiotherapy was oligo-progressive disease (70%) followed by symptom palliation. Eight (35%) of the treatments were delivered by stereotactic ablative body radiotherapy. Twelve (60%) patients had concurrent immunotherapy. Twenty of twenty-three (87%) adrenal lesions had an initial response to treatment with 12 (60%) maintaining local control until death or end of follow-up. Median adrenal-specific progression-free survival was 13 months. Four patients (17%) required salvage adrenalectomy. Symptom palliation was achieved in the majority of patients for which it was indicated and there were no grade three toxicities. The median time from radiotherapy to change of immunotherapy treatment was 4 months. Radiotherapy for melanoma adrenal metastasis is effective and deliverable. With the majority of patients achieving a palliative and clinically relevant durable response, adrenalectomy can be reserved as a salvage option.

Linking Cardiac and Extracardiac Sarcoidosis and Their Clinical Outcome: Serial 18f-FDG PET/CT Analysis in Patients with Systemic Cardiac Sarcoidosis

Linking Cardiac and Extracardiac Sarcoidosis and Their Clinical Outcome: Serial 18f-FDG PET/CT Analysis in Patients with Systemic Cardiac Sarcoidosis

Role of serial cardiac 18F-FDG PET-MRI in Anderson\u2013Fabry disease: a pilot study

AimWe investigated the value of serial cardiac 18F-FDG PET-MRI in Anderson–Fabry disease (AFD) and the potential relationship of imaging results with FASTEX score.Methods and resultsThirteen AFD patients underwent cardiac 18F-FDG PET-MRI at baseline and follow-up. Coefficient of variation (COV) of FDG uptake and FASTEX score were assessed. At baseline, 9 patients were enzyme replacement therapy (ERT) naïve and 4 patients were under treatment. Two patients presented a FASTEX score of 0 indicating stable disease and did not show any imaging abnormality at baseline and follow-up PET-MRI. Eleven patients had a FASTEX score > 20% indicating disease worsening. Four of these patients without late gadolinium enhancement (LGE) and with normal COV at baseline and follow-up had a FASTEX score of 35%. Three patients without LGE and with abnormal COV at baseline and follow-up had a FASTEX score ranging from 30 to 70%. Three patients with LGE and abnormal COV at baseline and follow-up had a FASTEX score between 35 and 75%. Finally, one patient with LGE and normal COV had a FASTEX score of 100%. Of the 12 patients on ERT at follow-up, FASTEX score was significantly higher in those 4 showing irreversible cardiac injury at baseline compared to 8 with negative LGE (66 ± 24 vs. 32 ± 21, p = 0.03).Conclusion18F-FDG PET-MRI may be effective to monitor cardiac involvement in AFD.

Cardiac 18F-FDG Positron Emission Tomography: An Accurate Tool to Monitor In vivo Metabolic and Functional Alterations in Murine Myocardial Infarction.

Cardiac monitoring after murine myocardial infarction, using serial non-invasive cardiac 18F-FDG positron emissions tomography (PET) represents a suitable and accurate tool for in vivo studies. Cardiac PET imaging enables tracking metabolic alterations, heart function parameters and provides correlations of the infarct size to histology. ECG-gated 18F-FDG PET scans using a dedicated small-animal PET scanner were performed in mice at baseline, 3, 14, and 30 days after myocardial infarct (MI) by permanent ligation of the left anterior descending (LAD) artery. The percentage of the injected dose per gram (%ID/g) in the heart, left ventricular metabolic volume (LVMV), myocardial defect, and left ventricular function parameters: end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and the ejection fraction (EF%) were estimated. PET assessment of the defect positively correlates with post-infarct histology at 3 and 30 days. Infarcted murine hearts show an immediate decrease in LVMV and an increase in %ID/g early after infarction, diminishing in the remodeling process. This study of serial cardiac PET scans provides insight for murine myocardial infarction models by novel infarct surrogate parameters. It depicts that serial PET imaging is a valid, accurate, and multimodal non-invasive assessment.

Prognostic Value of the Pace of Tumor Progression as Assessed by Serial 18F-FDG PET/CT Scan and Liquid Biopsy in Refractory Colorectal Cancer: The CORIOLAN Trial

Simple SummaryManagement of chemorefractory colorectal cancer patient is challenging, and reliable tools which can predict individual patient prognosis and help the decision making are needed. In this study, we hypothesized that the natural pace of cancer growth and progression, as assessed by early changes of a number of imaging and circulating biomarkers which are surrogates of tumor burden (i.e., metabolically active tumor volume, carcinoembryonic antigen, circulating tumor cells and circulating tumor DNA), could predict patient prognosis. By prospectively recruiting 47 eligible patients who had measurements of these biomarkers taken two weeks apart in the absence of any active anti-cancer treatment, we failed to demonstrate our hypothesis. On the other hand, we found that baseline assessment of the same biomarkers was associated with survival outcomes. Larger studies are needed to confirm these findings and translate them into applications for clinical practice.Introduction: Decision making in refractory colorectal cancer (rCRC) is challenging, with limited data available to predict patient outcome. We conducted a study to assess the pace of cancer progression as a potential prognostic and decision tool. Methods: CORIOLAN was a prospective, single-center, single-arm trial recruiting refractory CRC patients with an ECOG performance status of ≤1 and an estimated life expectancy of ≥12 weeks. 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and blood sample collection were carried out at baseline and after 2 weeks with no cancer treatment given between these timepoints. The primary objective was to evaluate the association between pace of cancer progression as defined by changes of the whole-body metabolically active tumor volume (WB-MATV) and overall survival (OS). Exploratory objectives included evaluation of the prognostic value of circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs) and carcinoembryonic antigen (CEA). Results: 47 eligible patients who had received a median number of 5 (range 2–8) prior treatments were enrolled. At the time of analysis, 45 deaths had occurred, with 26% of patients dying within 12 weeks. The median OS was 6.3 months (range 0.4–14.3). The median relative delta between WB-MATV at baseline and 2 weeks was +21%. Changes of WB-MATV, however, failed to predict OS (hazard ratio (HR) 1.3, p = 0.383). Similarly, no association was observed between changes of any of the circulating biomarkers investigated and prognosis. By contrast, high WB-MATV (4.2 versus 9.4 months; HR 3.1, p = 0.003), high CEA (4.4 versus 7.0 months; HR 1.9, p = 0.053), high cfDNA (4.7 versus 7.0 months; HR 2.2, p = 0.015) and high CTC count (3.3 versus 7.5 months; HR 6.5, p < 0.001) at baseline were associated with worse OS. Conclusions: In this study, approximately 1 out of 4 refractory CRC patients who were judged to have a life expectancy >12 weeks actually died within 12 weeks. Baseline assessment of WB-MATV, cfDNA, CTCs and CEA, but not early change evaluation of the same, may help to refine patient prognostication and guide management decisions.

Surveillance of Clinically Complete Responders Using Serial 18F-FDG PET/CT Scans in Patients with Esophageal Cancer After Neoadjuvant Chemoradiotherapy

Active surveillance for patients with esophageal cancer and a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is being studied. Active surveillance requires accurate clinical response evaluations. 18F-FDG PET/CT might be able to detect local tumor recurrence after nCRT as soon as the esophagus recovers from radiation-induced esophagitis. The aims of this study were to assess the value of serial 18F-FDG PET/CT scans for detecting local recurrence in patients beyond 3 mo after nCRT and to determine when radiation-induced esophagitis has resolved. Methods: This retrospective multicenter study included patients who had cCR after nCRT, who initially declined surgery, and who subsequently underwent active surveillance. Clinical response evaluations included 18F-FDG PET/CT, endoscopic biopsies, and endoscopic ultrasound with fine-needle aspiration at regular intervals. SUVmax normalized for lean body mass (SULmax) was measured at the primary tumor site. The percentage change in SULmax (Δ%SULmax) between the last follow-up scan and the scan at 3 mo after nCRT was calculated. Tumor recurrence was defined as biopsy-proven vital tumor at the initial tumor site. Results: Of 41 eligible patients, 24 patients had recurrent disease at a median of 6.5 mo after nCRT and 17 patients remained cancer free during a median follow-up of 24 mo after nCRT. Five of 24 patients with tumor recurrence had sudden intense SULmax increases of greater than 180%. In 19 of 24 patients with tumor recurrence, SULmax gradually increased (median Δ%SULmax, +18%), whereas SULmax decreased (median Δ%SULmax, -12%) in patients with ongoing cCR (P < 0.001, independent-samples t test). In patients with ongoing cCR, SULmax was lowest at 11 mo after nCRT. Conclusion: Serial 18F-FDG PET/CT might be a useful tool for detecting tumor recurrence during active surveillance. In patients with ongoing cCR, the lowest SULmax was reached at 11 mo after nCRT, suggesting that radiation-induced esophagitis had mostly resolved by that time. These findings warrant further evaluation in a larger cohort.

Prediction of Anal Cancer Recurrence After Chemoradiotherapy Using Quantitative Image Features Extracted From Serial 18F-FDG PET/CT.

We extracted image features from serial 18F-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) scans of anal cancer patients for the prediction of tumor recurrence after chemoradiation therapy (CRT). Seventeen patients (4 recurrent and 13 non-recurrent) underwent three PET/CT scans at baseline (Pre-CRT), in the middle of the treatment (Mid-CRT) and post-treatment (Post-CRT) were included. For each patient, Mid-CRT and Post-CRT scans were aligned to Pre-CRT scan. Comprehensive image features were extracted from CT and PET (SUV) images within manually delineated gross tumor volume, including geometry features, intensity features and texture features. The difference of feature values between two time points were also computed and analyzed. We employed univariate logistic regression model, multivariate model, and naïve Bayesian classifier to analyze the image features and identify useful tumor recurrent predictors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of the prediction. In univariate analysis, six geometry, three intensity, and six texture features were identified as significant predictors of tumor recurrence. A geometry feature of Roundness between Post-CRT and Pre-CRT CTs was identified as the most important predictor with an AUC value of 1.00 by multivariate logistic regression model. The difference of Number of Pixels on Border (geometry feature) between Post-CRT and Pre-CRT SUVs and Elongation (geometry feature) of Post-CRT CT were identified as the most useful feature set (AUC = 1.00) by naïve Bayesian classifier. To investigate the early prediction ability, we used features only from Pre-CRT and Mid-CRT scans. Orientation (geometry feature) of Pre-CRT SUV, Mean (intensity feature) of Pre-CRT CT, and Mean of Long Run High Gray Level Emphasis (LRHGLE) (texture feature) of Pre-CRT CT were identified as the most important feature set (AUC = 1.00) by multivariate logistic regression model. Standard deviation (intensity feature) of Mid-CRT SUV and difference of Mean of LRHGLE (texture feature) between Mid-CRT and Pre-CRT SUVs were identified as the most important feature set (AUC = 0.86) by naïve Bayesian classifier. The experimental results demonstrated the potential of serial PET/CT scans in early prediction of anal tumor recurrence.

Anti-inflammatory effect of statin is continuously working throughout use: a prospective three time point 18F-FDG PET/CT imaging study.

No data exist whether statins have robust anti-inflammatory effects of atherosclerotic plaques primarily during the early treatment period or continuously throughout use. This prospective three time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study of the carotid artery assessed anti-inflammatory effects of statin during the early treatment period (initiation to 3months) and late treatment period (3months to 1year) and their correlation with lipid and inflammatory profile changes during a year of therapy. Nine statin-naïve stable angina patients with inflammatory carotid plaques received 20mg/day atorvastatin after undergoing initial 18F-FDG PET/CT scanning of carotid arteries and ascending thoracic aorta, and then completed serial 18F-FDG PET/CT imaging at 3 and 12months whose data were analyzed. The primary outcome was the inter-scan percent change in target-to-background ratio (ΔTBR) within the index vessel. At 3months of atorvastatin treatment, mean serum low-density lipoprotein cholesterol (LDL-C) level decreased by 36.4% to < 70mg/dL (p = 0.001) and mean serum high-density lipoprotein cholesterol level increased to > 40mg/dL (p = 0.041), with both maintained with no further reduction up to 1year (p = 0.516 and 0.715, respectively) while mean serum high sensitivity C-reactive protein level only numerically decreased (p = 0.093). The index vessel ΔTBR showed continuous plaque inflammation reduction over 1year, by 4.4% (p = 0.015) from the initiation to 3rd months and 6.2% (p = 0.009) from 3rd months to 1 year, respectively, without correlation with lipid profile changes. The ΔTBR of the bilateral carotid arteries and ascending aorta also continuously decreased from 3months to 1year. Three time point 18F-FDG PET/CT imaging demonstrates that statin's anti-inflammatory effect continues throughout its use up to 1year, even though yielding stable below-target plasma LDL-C levels at 3months.

Prediction of response to immune checkpoint inhibitor therapy using 18F-FDG PET/CT in patients with melanoma.

We aimed to assess serial 18F-FDG PET/CT imaging according to morphological (RECIST1.1, iRECIST) and functional (PERCIST, PECRIT) criteria to predict clinical response to therapy in patients with advanced melanoma receiving immune checkpoint blocking agents.Retrospective data collection and analysis was done for 37 patients with unresectable metastatic cutaneous melanoma eligible for immunotherapy (cycles: 4 for ipilimumab and pembrolizumab/ 6 for nivolumab).18F-FDG PET/CT imaging was performed prior to (18F-FDG PET/CT 0) and 14 weeks after ICI onset (18F-FDG PET/CT 1). Some cases during the follow-up required imaging (18F-FDG PET/CT 2). Assessment of patient response to treatment was done according to RECIST1.1, iRECIST, PERCIST and PECRIT criteria.Among 37 assessed patients, 27 had 1 line of ICI, 8 had 2 lines of ICI and 2 patients had 3 lines of ICI: total of 49 PET/CTs. Mean time between initiation of ICI and 18F-FDG PET/CT (1 or 2) were respectively 13.82 ± 4.32 and 24.73 ± 9.53 weeks. Time between 18F-FDG PET/CT 1 and 18F-FDG PET/CT 2 was at mean +/− SD: 11.19w ± 5.59. Median PFS was 29.62 months (range 22.52–36.71) (P = .001: RECIST 1.1), (P < .0001: iRECIST), (P = .000: PERCIST), (P = .072: PECRIT). Median OS was 36.62 months (30.46–42.78) (P = .005: RECIST 1.1), (P < .0001: iRECIST), (P = .001: PERCIST), (P = .082 PECRIT).18F-FDG PET/CT could detect eventual ICI-response in patients with metastatic melanoma undergoing ICI using iRECIST and PERCIST criteria

Pre-existing SIV infection decreases cytokine responses by T cells in lung during the early stages of M. tuberculosis co-infection

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death among HIV+ individuals. The precise mechanisms by which HIV impairs the immune response to subsequent Mtb infection are unknown. We previously established a model of co-infection in Mauritian cynomolgus macaques (MCM). We found SIV/Mtb co-infected MCM had rapidly progressive TB and reached humane endpoint by 12 weeks post-Mtb infection. We hypothesized that pre-existing SIV impacts T cell responses at the early stages of Mtb infection. We infected MCM with SIVmac239 intrarectally and 6 months later co-infected with a low dose of Mtb. SIV-naïve MCM were infected with Mtb alone as controls. Animals were monitored by clinical parameters, culturing bacilli in gastric and bronchoalveolar lavages, and serial 18F-FDG PET/CT imaging. Six weeks after Mtb infection, animals were necropsied and immune responses in the lung were measured by flow cytometry. The two groups exhibited similar TB disease at time of necropsy. Total bacterial burden was remarkably high in both SIV-naïve and SIV/Mtb groups, although co-infected animals tended to have more bacteria in lung tissue. At sites of Mtb infection, SIV/Mtb co-infected animals had fewer CD4+ T cells and significantly more CD8+ T cells. TNFα production by these CD4+ and CD8+ T cells was decreased. Taken together, pre-existing SIV decreases the quality of cytokine responses by T cell at sites of Mtb infection during the early stages of TB disease. This appears to be a critical time point at which the immunologic defect from pre-existing SIV infection begins to impact the arc of TB disease.

Impact of different image reconstructions on PET quantification in non-small cell lung cancer: a comparison of adenocarcinoma and squamous cell carcinoma

Positron emission tomography (PET) using 18F-fludeoxyglucose (18F-FDG) is an established imaging modality for tumor staging in patients with non-small cell lung cancer (NSCLC). There is a growing interest in using 18F-FDG PET for therapy response assessment in NSCLC which relies on quantitative PET parameters such as standardized uptake values (SUV). Different reconstruction algorithms in PET may affect SUV. We sought to determine the variation of SUV in patients with NSCLC when using ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) in latest-generation digital PET/CT, including a subanalysis for adenocarcinoma and squamous cell carcinoma. A total of 58 patients (34 = adenocarcinoma, 24 = squamous cell carcinoma) who underwent a clinically indicated 18F-FDG PET/CT for staging were reviewed. PET images were reconstructed with OSEM and BSREM reconstruction with noise penalty strength β-levels of 350, 450, 600, 800 and 1200. Lung tumors maximum standardized uptake value (SUVmax) were compared. Lung tumors SUVmax were significantly lower in adenocarcinomas compared to squamous cell carcinomas in all reconstructions evaluated (all p < 0.01). Comparing BSREM to OSEM, absolute SUVmax differences were highest in lower β-levels of BSREM with + 2.9 ± 1.6 in adenocarcinoma and + 4.0 ± 2.9 in squamous cell carcinoma (difference between histology; p-values > 0.05). There was a statistically significant difference of the relative increase of SUVmax in adenocarcinoma (mean + 34.8%) and squamous cell carcinoma (mean 23.4%), when using BSREM350 instead of OSEMTOF (p < 0.05). In NSCLC the relative change of SUV when using BSREM instead of OSEM is significantly higher in adenocarcinoma as compared to squamous cell carcinoma. The impact of BSREM on SUV may vary in different histological subtypes of NSCLC. This highlights the importance for careful standardization of β-value used for serial 18F-FDG PET scans when following-up NSCLC patients.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis.

Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial 18F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUVmax), average SUVmean (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient. Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results. Conclusions: Pretreatment volume-based 18F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study.