Decrease In FDG Uptake Research Articles

SDPS-08 OSSEOUS METASTASES IN H3G34-MUTANT DIFFUSE HEMISPHERIC GLIOMAS

Abstract Subset of patients with H3G34 gliomas may present with extra-CNS metastasis further complicating both diagnosis and treatment. We describe a case of a 19-year-old female presenting initially with focal motor seizure in right leg along with leg pain. MRI of the leg showed an ill-defined right distal femur expansile osteolytic lesion with central fluid signal, thick rim enhancement, endosteal scalloping, cortical invasion, and smooth enhancing periosteal reaction/soft tissue extension associated with surrounding enhancing marrow signal abnormality worrisome for lesion extension. Contrast brain MRI exhibited multiple frontal and partial lobe T2 FLAIR hyperintense lesions. The largest lesion demonstrated contrast enhancement, internal foci of restricted diffusion, and a focus of intratumoral hemorrhage. A whole-body PET/CT showed intensely FDG-avid lytic lesion in the right distal femur, with FDG activity along the biopsy tract. Hypermetabolic lytic metastases to the right femoral head and mid-sacral body were also observed. A craniotomy with brain lesion biopsy two months later indicated preliminary histopathology of malignant small round blue cell neoplasm. A biopsy from the distal right femur was non-diagnostic of malignancy but a sacral bone biopsy reported malignant small blue cell neoplasm, consistent with involvement by the patient's known cranial neoplasm. Final pathological diagnosis including molecular diagnostics was consistent with WHO grade 4 IDH-wildtype H3G34 mutant diffuse hemispheric glioma with osseous metastases. Patient was treated with chemoradiotherapy with temozolomide (TMZ). Following the sixth cycle of TMZ, MRI brain imaging was stable. Apart from holocephalic headaches, the patient had no significant medication side effects and was seizure-free. A second whole-body PET scan showed improvement and interval decrease in FDG uptake of the sacrum and right femoral head. Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate screening and diagnostic methodologies.

CTNI-27. MULTI-CENTER, PHASE 2 STUDY EVALUATING THE PHARMACOKINETICS, SAFETY AND PRELIMINARY EFFICACY OF PAXALISIB IN NEWLY DIAGNOSED ADULT PATIENTS WITH UNMETHYLATED GLIOBLASTOMA (GBM)

Abstract NCT03522298 was an open-label, multi-center, 2-stage trial designed to establish the maximum tolerated dose (MTD) for once-daily (QD) paxalisib dosing (Stage 1), then evaluate pharmacokinetics(PK) and safety and explore efficacy (Stage 2). Eligible patients had undergone surgical resection and chemoradiotherapy (EORTC 26981–22981/NCIC CE3), had a life expectancy of ³ 12 weeks and were progression free before starting adjuvant paxalisib. Stage 1 used a standard 3 + 3 dose-escalation design to determine the MTD. Stage 2 was a two-arm, open-label, expansion cohort with patients randomized 1:1 to receive paxalisib at the MTD under fed or fasted conditions. In both stages, treatment comprised daily paxalisib administered in continuous 28-day cycles, until disease progression or unacceptable toxicity. Patients (n = 30; 70.0% males, mean age 58.5 years, mean 3.75 months since diagnosis) received paxalisib for a mean duration of 99 (9-833) days. In Stage 1 (n = 9), an MTD of 60mg was established on the dose-limiting toxicities of hyperglycemia (n = 1) and stomatitis (n = 1) at 75mg. Paxalisib was well-tolerated with no unexpected safety signals. Adverse events (37%) or progressive disease (33%) were the primary reasons for treatment discontinuation. At the MTD, the PK profile was linear and dose-proportional with no differences in Tmax and elimination half-life under fed/fasted conditions. Ten patients underwent FDG-PET imaging, 8 (80%) had a decrease in FDG uptake on Day 3 and/or Day 7 in Cycle 1; 4 (40%) had a metabolic partial response. From date of diagnosis, progression free survival (mRANO, investigator review) was 8.6 months and overall survival was 15.7 months. Primary study outcomes (1) MTD of 60mg was established for QD dosing and (2) PK and safety were consistent with prior clinical experience. Preliminary efficacy signals were encouraging and further investigation of paxalisib 60mg QD in newly diagnosed and recurrent GBM is ongoing in a pivotal trial (GBM AGILE, NCT03970447).

280O Pharmacokinetics and pharmacodynamics of paxalisib in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status: Final phase II study results

Paxalisib is being developed for the treatment of glioblastoma multiforme (GBM). Post hoc analysis of phase 1 fluorodeoxyglucose-positron emission tomography (FDG-PET) scans suggested that paxalisib crosses the blood-brain barrier with a uniform distribution throughout the brain. The recently completed phase 2 trial (NCT03522298) enrolled patients with newly diagnosed GBM with unmethylated MGMT promoter status following surgical resection and chemotherapy (Stupp Regimen). Study outcomes comprised maximum tolerated dose (MTD), safety, preliminary efficacy, pharmacokinetics (PK) at the MTD under fed and fasted conditions and change in FDG-PET uptake in patients with measurable disease. Patients (n=30; 70.0% males, mean age 58.5 years) received between 1 and 29 treatment cycles. At the MTD (60 mg/day), paxalisib prolonged median progression free survival (8.4 months [RANO], 8.6 months [mRANO]) and improved median overall survival (15.7 months). Paxalisib was steadily absorbed (median Tmax 2.5 and 4 hours postdose) and declined with a mean elimination half-life ranging from 20.2 to 29.0 hours. Mean half-life (20.2 to 29.0 hours) was similar across dose levels and under fed and fasted conditions. Systemic exposure to paxalisib appeared slightly higher for the 60 mg fed status compared to 60 mg fasted status. Comparison of fed versus fasted treatment was statistically significant for Cmax at the 90% level (geometric least squares mean ratios: AUC0-last 1.33, AUC0-inf 1.06, and Cmax 1.52). Ten patients underwent FDG-PET imaging, 8 (80%) had a decrease in FDG uptake on Day 3 and/or Day 7 in Cycle 1 and 4 (40%) had a metabolic partial response. PK parameters were consistent with prior clinical experience and there was no evidence of a deviation from dose-proportionality. At the MTD FDG-PET data provide evidence that paxalisib has the ability to exert biological effect in tumour tissue, irrespective of fed or fasted status. Further evaluation is ongoing in GBM AGILE (NCT03970447).

Evaluation of 18F-FMISO PET and 18F-FDG PET Scans in Assessing the Therapeutic Response of Patients With Metastatic Colorectal Cancer Treated With Anti-Angiogenic Therapy.

IntroductionTumor hypoxia and angiogenesis are implicated in tumor growth and metastases, and anti-angiogenic therapies have an important role in treating patients with metastatic colorectal cancer. However, the prevalence of hypoxia has not been fully evaluated in colorectal liver metastases, and hypoxic response to anti-angiogenic therapy has not been clearly established. The aims of the study were to evaluate the changes seen on 18F-FMISO and 18F-FDG PET scans in patients treated with anti-angiogenic therapy, and to correlate these measures of hypoxia and metabolism with clinical outcomes, and blood biomarkers of angiogenesis.MethodsPatients with metastatic colorectal carcinoma planned for treatment with bevacizumab and chemotherapy received routine staging investigations prior to any treatment, including a FDG PET scan. A FMISO PET scan was performed within 4 weeks of staging tests, with blood specimens collected at that time for serum VEGF and osteopontin measurement. Follow-up FDG and FMISO scans were performed after 1 cycle of treatment. Results were compared to response (RECIST), progression free survival (PFS), and overall survival (OS).ResultsA total of 15 patients were recruited into this prospective trial, of which 13 patients were evaluable for assessment of treatment follow-up. Baseline FDG uptake was higher than FMISO uptake, and there was a significant decrease in FDG uptake (SUVmax and TGV) but not FMISO uptake (SUVmax and TNR) after treatment. There was a positive correlation between FDG and FMISO SUVmax on both baseline and post-treatment PET scans. Blood biomarkers of serum VEGF and osteopontin were significantly correlated with the FDG and FMISO PET parameters.ConclusionsThis study shows that hypoxia in metastatic colorectal cancer, assessed by FMISO PET, shows minor changes following initial treatment with anti-angiogenic therapy, but is associated with therapeutic response. FDG PET uptake changes (SUVmax, TLG) are also associated with response to anti-angiogenic therapy. These findings demonstrate the interplay between tumor metabolism and hypoxic regulation following anti-angiogenic treatment of metastatic colorectal cancer.

18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress.

In cognitively normal patients, mild hyperglycemia selectively decreases 18F-Fluorodeoxyglucose (FDG) uptake in the posterior brain, reproducing Alzheimer disease pattern, hampering the diagnostic accuracy of this widely used tool. This phenomenon might involve either a heterogeneous response of glucose metabolism or a different sensitivity to hyperglycemia-related redox stress. Indeed, previous studies reported a close link between FDG uptake and activation of a specific pentose phosphate pathway (PPP), triggered by hexose-6P-dehydrogenase (H6PD) and contributing to fuel NADPH-dependent antioxidant responses in the endoplasmic reticulum (ER). To clarify this issue, dynamic positron emission tomography was performed in 40 BALB/c mice four weeks after administration of saline (n = 17) or 150 mg/kg streptozotocin (n = 23, STZ). Imaging data were compared with biochemical and histological indexes of glucose metabolism and redox balance. Cortical FDG uptake was homogeneous in controls, while it was selectively decreased in the posterior brain of STZ mice. This difference was independent of the activity of enzymes regulating glycolysis and cytosolic PPP, while it was paralleled by a decreased H6PD catalytic function and enhanced indexes of oxidative damage. Thus, the relative decrease in FDG uptake of the posterior brain reflects a lower activation of ER-PPP in response to hyperglycemia-related redox stress in these areas.

18F-FDG PET-guided diffusion tractography reveals white matter abnormalities around the epileptic focus in medically refractory epilepsy: implications for epilepsy surgical evaluation

BackgroundHybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning.MethodsFDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the EF. Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was evaluated by a senior neurologist.ResultsIn over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery.ConclusionsWe demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery.

Clinical Characteristics, Treatment Patterns and Outcomes of Solitary Plasmacytoma - a Multicenter Retrospective Cohort Study

Background: Solitary plasmacytoma (SPC) is a rare plasma cells disorder, which may present as a single bone lesion or an extramedullary plasmacytoma. High dose radiotherapy may be curative, yet most patients eventually develop Multiple Myeloma (MM). Due to rarity of the disease, there is uncertainty regarding the optimal treatment strategy, especially in patients that present with known risk factors. The role of adjuvant anti-myeloma therapy is still under debate, whereas few studies have reported efficacy of novel agents. We aimed to explore clinical characteristics and treatment patterns and to identify predictors for relapse and progression to myeloma in a real world setting. Methods: Consecutive patients, diagnosed and treated for solitary plasmacytoma in 13 centers, between 2008 and 2019 (defined by the IMWG criteria) were identified, based on medical centers patient registries and pathological reports. Patient's medical charts were reviewed, and data regarding patient and disease characteristics, treatment regimen, and clinical endpoints, focusing on response to treatment and time to disease progression were documented. The treatment response categories were defined according to the IMWG criteria. Results: 62 patients (pts) were identified. Baseline characteristics and workup are detailed in the table. Median follow-up was 39 months (mo) (IQR: 13.5, 63.3). Fifty nine pts (95.2%) were treated with radiotherapy, with a median dose of 45.0 Gy (range: 30-54 Gy); radiotherapy dose was 45-54 in 31 pts, < 45Gy in 11 pts. Twenty pts (33.9%) underwent surgery in addition to radiotherapy, 3 more pts underwent a surgery alone. The median time to radiotherapy since diagnosis was 2.7 months (range: 1day-18.2 months), 8 pts received any anti-myeloma therapy for treatment of plasmacytoma including Melphalan/dexamethasone (n=1), bortezomib based induction followed by ASCT (n=2), VD/VTD (n=2) and KRD (n=1). Among 25 patients with evaluable post-therapy PET-CT response (performed 12 months post radiotherapy), 26% had no remaining FDG uptake, 20% had a 50% or greater decrease in FDG uptake. Among 40 patients with CT or MRI post therapy assessment, 20% had disappearance of SPC, 27% had ≥50% reduction, 7% had <50% reduction and 25% remained without change. Non-bone SPC were more likely to achieve CR than bone SPCs, 86% vs 29%, respectively, p=0.021. During the follow-up period, 16 pts (25.8%) experienced evolution to MM (15 pts had bony and 1 soft tissue plasmacytoma in diagnosis). Among patients with bone SPC (n=49), 30.5% evolved to MM. A total of 6 pts had a recurrence of SPC (5 pts had a bony and 1 patient upper aerodigestive plasmacytoma in diagnosis). 5 pts died (3 without recurrence or evolution to MM). Median time to plasmacytoma recurrence in pts that achieved CR was 36.7 mo (range: 3 -67.9 mo); Median time of evolution to MM was 37.5 mo (range: 6.7-87.2 mo). Progression free survival (PFS) was 67.7 mo for all pts (Fig1A), 48 mo for bone SPC and was not reached for non-bone SPC (p=0.11) (Fig1B). Median overall survival was not reached. Overall survival at median follow-up was 93.6%. Notably, all 8 pts who were treated with anti-myeloma therapy had a bony plasmacytoma and received radiotherapy in addition. None of these pts had recurrence of plasmacytoma or evolution to MM. Of the 11 pts that had SPC in an upper aerodigestive tract site, none evolved to MM; 10 of these pts were treated with only radiotherapy, one had a plasmacytoma recurrence in the same site. Conclusions: We present real world data of a multicenter patient cohort with SPC. As previously suggested, prognosis is more favorable for none bone SPCs. Though numbers are modest, our analysis suggests a benefit of the early addition of systemic therapy to standard radiotherapy for patients with solitary bone plasmacytoma. Disclosures Yael: Janssen: Consultancy; Amgen: Consultancy, Research Funding; Neopharm: Consultancy; Takeda: Consultancy; Madison: Consultancy; VBL Therapeutics: Employment.

Utility of positron emission tomography/computed tomography (PET/CT) imaging in the evaluation of sarcomas: A systematic review.

Sarcomas are a heterogeneous group of malignant tumours with variable clinical outcomes. Their presence in multiple body locations represents significant diagnostic and therapeutic challenges. Positron emission tomography/computed tomography (PET/CT) is an imaging tool that provides semiquantitative measurements of radiotracer concentration in tissue, such as SUVmax (standardised uptake value) and is increasingly used in clinical practice. This systematic review aims to evaluate the utility of PET/CT in sarcoma grading and prognostication, evaluation of treatment response, staging and restaging. Relevant studies published from January 2003 to August 2017 evaluating the utility of PET/CT in sarcoma grading and prognostication, staging, evaluation of treatment response and restaging were systematically searched for in scientific databases (e.g. PubMed, Medline and Embase) using key terms, including "soft tissue sarcoma," "osteosarcoma," "utility" and "PET/CT". Additionally, references of identified studies were reviewed. Study quality was assessed by "Quality Assessment of Diagnostic Accuracy Studies". A total of 12 prospective studies (level II to III evidence) were included in the review for tumour grading and prognostication. There was a strong correlation between SUV and tumour grade where majority of intermediate/ high-grade STS have a significantly higher SUVmax. PET/CT has also shown potential in prognostication where decrease in SUVmax correlated with recurrence-free survival in both osteosarcoma and STS. Furthermore, 8 prospective trials of level II to IV evidence according to Oxford Centre of Evidence-based Medicine (CEBM) demonstrated the use of PET/CT in early identification of patients who will respond to treatment where ≥60% decrease in FDG uptake resulted in sensitivity and specificity of 100% and 71% respectively for assessment of histopathologic response. 11 retrospective trials (level III to IV evidence) reported on the use of PET/CT in staging and restaging with heterogeneous results. Overall, higher quality evidence demonstrated PET/CT to be an important contributor towards sarcoma grading, prognostication and evaluation of treatment response. Larger prospective trials will be helpful to further establish the clinical value of PET/CT in sarcoma staging and restaging.

Very Early Response Evaluation by PET/MR in Patients with Lung Cancer-Timing and Feasibility.

Purpose: With the increasing number of therapy options available for patients with lung cancer, early response evaluation is needed. We performed this pilot study to assess the feasibility of early, repeated Positron emission tomography-magnetic resonance (PET/MR), the impact of timing and the capability for response prediction in lung tumors during chemotherapy. Methods: Patients with stage IV non-small cell lung cancer referred for chemotherapy were prospectively recruited. Fluorine-18-Fluorodeoxyglucose(18F-FDG)-PET/MR scans were performed prior to, during and after the first or second cycle of chemotherapy. Primary tumors were defined on all scans and size, FDG-uptake and apparent diffusion coefficient (ADC) were measured. Early response was described over time and a Standard Linear Mixed Model was applied to analyze changes over time. Results: 45 FDG-PET/MR scans were performed in 11 patients. Whereas the overall changes measured by ADC did not change significantly, there was an overall significant decrease in FDG-uptake from pre to post treatment scans. There was no difference in the FDG-uptake measured 1 or 3 weeks after therapy, but uptake measured 2 weeks after therapy differed from measurements at week 3. Changes measured in patients scanned during the first treatment cycle appeared more pronounced than during the second cycle. Conclusions: This pilot study indicates that response evaluation shortly after initiation of chemotherapy appears concordant with later evaluation and probably more reliable than evaluation midway between cycles. Responses during or after the first cycle of chemotherapy rather than during subsequent cycles are likely to be more readily measured.

Famous faces and voices: Differential profiles in early right and left semantic dementia and in Alzheimer's disease

BackgroundFamous face and voice recognition is reported to be impaired both in semantic dementia (SD) and in Alzheimer's Disease (AD), although more severely in the former. In AD a coexistence of perceptual impairment in face and voice processing has also been reported and this could contribute to the altered performance in complex semantic tasks. On the other hand, in SD both face and voice recognition disorders could be related to the prevalence of atrophy in the right temporal lobe (RTL). ObjectiveThe aim of the present study was twofold: (1) to investigate famous faces and voices recognition in SD and AD to verify if the two diseases show a differential pattern of impairment, resulting from disruption of different cognitive mechanisms; (2) to check if face and voice recognition disorders prevail in patients with atrophy mainly affecting the RTL. MaterialsTo avoid the potential influence of primary perceptual problems in face and voice recognition, a pool of patients suffering from early SD and AD were administered a detailed set of tests exploring face and voice perception. Thirteen SD (8 with prevalence of right and 5 with prevalence of left temporal atrophy) and 25 CE patients, who did not show visual and auditory perceptual impairment, were finally selected and were administered an experimental battery exploring famous face and voice recognition and naming. Twelve SD patients underwent cerebral PET imaging and were classified in right and left SD according to the onset modality and to the prevalent decrease in FDG uptake in right or left temporal lobe respectively. Correlation of PET imaging and famous face and voice recognition was performed. ResultsResults showed a differential performance profile in the two diseases, because AD patients were significantly impaired in the naming tests, but showed preserved recognition, whereas SD patients were profoundly impaired both in naming and in recognition of famous faces and voices. Furthermore, face and voice recognition disorders prevailed in SD patients with RTL atrophy, who also showed a conceptual impairment on the Pyramids and Palm Trees test more important in the pictorial than in the verbal modality.Finally, in 12SD patients in whom PET was available, a strong correlation between FDG uptake and face-to-name and voice-to-name matching data was found in the right but not in the left temporal lobe. DiscussionThe data support the hypothesis of a different cognitive basis for impairment of face and voice recognition in the two dementias and suggest that the pattern of impairment in SD may be due to a loss of semantic representations, while a defect of semantic control, with impaired naming and preserved recognition might be hypothesized in AD. Furthermore, the correlation between face and voice recognition disorders and RTL damage are consistent with the hypothesis assuming that in the RTL person-specific knowledge may be mainly based upon non-verbal representations.

Metabolic response assessment with 18F-FDG PET/CT: inter-method comparison and prognostic significance for patients with non-small cell lung cancer.

ObjectiveThis study aimed to (1) compare the agreement of two evaluation methods of metabolic response in patients with non-small cell lung cancer (NSCLC) and determine their prognostic value and (2) explore an optimal cutoff of metabolic reduction to distinguish a more favorable subset of responders.MethodsThis is a secondary analysis of prospective studies. Enrolled patients underwent 18F-PET/CT within 2 weeks before, during, and months after radiotherapy (post-RT). Metabolic response was assessed using both Peter MacCallum (PM) method of qualitative visual assessment and University of Michigan (UM) method of semiquantitative measurement. The agreement between two methods determined response, and their prediction of outcome was analyzed.ResultsForty-four patients with median follow-up of 25.2 months were analyzed. A moderate agreement was observed between PM- and UM-based response assessment (Kappa coefficient = 0.434), unveiling a significant difference in CMR rate (p = 0.001). Categorical responses derived from either method were significantly predictive of overall survival (OS) and progression-free survival (PFS) (p < 0.0001). Numerical percentage decrease of FDG uptake also showed significant correlations with survival, presenting a hazard ratio of 0.97 for both OS and PFS. A 75 % of SUV decrease was found to be the optimal cutoff to predict OS and 2-year progression.ConclusionsThere was a modest discrepancy in metabolic response rates between PM and UM criteria, though both could offer predictive classification for survival. The percentage decrease provides an ordinal value that correlates with prolonged survival, recommending 75 % as the optimal threshold at identifying better responders.

Imaging Requirements for Personalized Medicine: The Oncologists Point of View

While conventional chemotherapy regimens aim to be cytotoxic against proliferating cells, molecular targeted therapies are directed at specific cancer-associated pathways. To optimize cancer care, an early evaluation of treatment response is warranted for any tumor type - and for any treatment - by using conventional imaging modalities such as ultrasound, CT and MR, FDG-PET or specific radiotracer. FDG-PET is one of the most extensively and successfully used imaging modalities to achieve an early response evaluation. A high SUV-value is a surrogate for malignancy in terms of cancer care and a decrease in FDG-uptake after therapy is associated with treatment response and a favorable clinical outcome. Anyhow, the potential of PET reaches further. By providing metabolic information PET (with or without CT) can help to select patients for targeted therapy and to adapt treatment protocols. PET with FDG and maybe other, more specific PET tracers, promises to direct in a better way personalized cancer care and thus promote translational research. An interesting aspect of molecular imaging is the ability to achieve knowledge on distribution and expression levels of a given receptor. Hereby, imaging could help in guiding systemic treatment given a broad spectrum of radiotracers, detecting specific mutations at molecular level in vivo. From an oncologists point of view the concept of 'personalized medicine' should evolve to include 'personalized imaging' as well as 'personalized treatment' in order to optimize cancer care, reduce side effects and improve quality of life for cancer patients.

Correlation of 18F-FDG Avid Volumes on Pre–Radiation Therapy and Post–Radiation Therapy FDG PET Scans in Recurrent Lung Cancer

To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography ((18)F-FDG PET) before and after therapy in recurrent lung cancer. We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial (18)F-FDG PET examinations after therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUVmax) (≥50% of SUVmax) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUVmax. The VOI of pretherapy and posttherapy (18)F-FDG PET images were correlated for the extent of overlap. The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. VOI defined by the SUVmax-≥50% isocontour may be a biological target volume for escalated radiation dose.

A Phase I Study of an Agonist CD40 Monoclonal Antibody (CP-870,893) in Combination with Gemcitabine in Patients with Advanced Pancreatic Ductal Adenocarcinoma

This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunologic correlatives, and antitumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDA). Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1,000 mg/m(2) gemcitabine once weekly for three weeks with infusion of CP-870,893 at 0.1 or 0.2 mg/kg on day three of each 28-day cycle. CP-870,893 was well-tolerated; one dose-limiting toxicity (grade 4, cerebrovascular accident) occurred at the 0.2 mg/kg dose level, which was estimated as the MTD. The most common adverse event was cytokine release syndrome (grade 1 to 2). CP-870,893 infusion triggered immune activation marked by an increase in inflammatory cytokines, an increase in B-cell expression of costimulatory molecules, and a transient depletion of B cells. Four patients achieved a partial response (PR). 2-[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) showed more than 25% decrease in FDG uptake within primary pancreatic lesions in six of eight patients; however, responses observed in metastatic lesions were heterogeneous, with some lesions responding with complete loss of FDG uptake, whereas other lesions in the same patient failed to respond. Improved overall survival correlated with a decrease in FDG uptake in hepatic lesions (R = -0.929; P = 0.007). CP-870,893 in combination with gemcitabine was well-tolerated and associated with antitumor activity in patients with PDA. Changes in FDG uptake detected on PET/CT imaging provide insight into therapeutic benefit. Phase II studies are warranted.

Neuropsychological and neuroimaging phenotype induced by a CAMTA1 mutation

Background/Aims: CAMTA1 mutations have recently been reported in families with intellectual disability and/or non-progressive congenital ataxias. The objective of this study was to describe the neuropsychological and neuroimaging phenotype of CAMTA1 mutation. Methods: We performed neuropsychological examinations, MRI and FDG-PET imaging in three patients with autosomal dominant mild intellectual disabilities and ataxia induced by a CAMTA1 intragenic deletion at 1p36.31p36.23. Results: Neuropsychological tests showed similar findings in two patients, with low information processing speed, slow memory consolidation, phonological disorders, working memory deficits, but mainly preserved executive function. Bilateral parietal and medial temporal abnormalities were found on brain MRI. Diffuse parieto-occipital and local left temporo-parietal decrease of FDG uptake was observed on PET images. Conclusion: These results suggest that CAMTA1 mutation may induce an unusual neuropsychological profile and parieto-temporal developmental abnormalities. We recommend screening for CAMTA1 mutations in patients with autosomal dominant mild intellectual disability presenting with similar a phenotype.

FDG-PET/CT (PET) in the early prediction of benefit from first-line chemotherapy plus bevacizumab (bev) in metastatic colorectal cancer (mCRC).

e14531 Background: The conventional assessment of response according to RECIST seems not optimal to estimate the actual benefit from antiangiogenic agents. A recent experience suggests the potential role of PET in the early prediction of benefit from first-line chemotherapy in mCRC. The objective of the present study was to evaluate the metabolic PET response to one single cycle of chemotherapy plus bev in mCRC patients (pts). Methods: PET was carried out at baseline and on day 13 in 51 unresectable mCRC pts, treated with biweekly bev-containing regimens; computed tomography (CT) scan was performed at baseline and every 2 months. PET response was defined by &gt;15% decrease in FDG uptake in the dominant proportion of lesions, in the absence of metabolically progressive lesions. CT response was defined according to RECIST 1.0. Results: PET response rate was 73%. PET responders achieved longer PFS compared to PET non-responders (median PFS: 11.0 vs 8.3 months; HR=0.45 [95%CI 0.14-0.93] p=0.035). RECIST CT response rate was 62% and 57%, in PET responders and non-responders, respectively (p=0.76). At an exploratory analysis, among pts (N=15) reporting a RECIST-defined stable disease (SD), those with a percentage decrease in FDG uptake higher than the median value (&gt;33%) had significantly longer PFS in comparison to those with a lower PET response (median PFS: 9.4 vs 7.4 months; HR=0.2 [95%CI 0.005-0.24] p=0.0006). Conclusions: Early PET response, assessed after one single cycle of chemotherapy plus bev, predicts PFS, while it does not correlate with traditional RECIST response. In the subgroup of pts reporting a RECIST SD, the early reduction in FDG uptake correlates with PFS. On the basis of our results, early PET response on day 13th could representan early predictor of benefit from bev plus chemotherapy in mCRC.

Changes in the tumor glucose-uptake measured by 18F-FDG PET with two weeks of single-agent cetuximab in localized squamous cell carcinoma of the esophagus.

e15042 Background: Cetuximab (CET), an antibody directed against epidermal growth factor receptor (EGFR) has proved efficacy in squamous cell cancer (SCC) of the head and neck in vitro and in vivo by enhancing the activity of chemo- and radiotherapy. The aim was to investigate the early metabolic response in esophageal SCC induced by single agent CET. Methods: Patients with cT3 Nx esophageal SCC received single agent CET for two weeks (400mg/m2 i. v. d -15 followed by 250mg/m2 d -8) before entering a neoadjuvant dose escalation protocol of weekly cetuximab plus weekly oxaliplatin (starting dose level 45mg/m²; d1,8,15,22,29), plus 5-FU cont. i.v. (starting dose level 180mg/m²/d; d1-5, 8-12, 15-19, 22-26, 29-33) and radiotherapy (45Gy cumulative dose; 1.8Gy/d). Surgery was scheduled 4-6 weeks after chemoradiation (CRT). Tumor FDG uptake was assessed by PET at baseline, two weeks after start of CET and two weeks after start of CRT. Standard uptake values (SUV) of the two response PETs were compared with SUVs measured at baseline and correlated with the histopathological response data. Results: 11 patients are assessable for metabolic and histopathological response. Decreases in the SUVs two weeks after the start of CET compared with baseline SUV ranged from -16% to -70% (median -24%) and from 0% to -72% (median -39%) two weeks after start of CRT. Three patients were classified as complete histopathological responders. One patient had a subtotal (&lt;10% residual tumor) and three patients a moderate response (10-50% residual tumor). No histopathological response was seen in 4 patients. We found an association between FDG uptake decreases both after single agent CET and after two weeks of CRT and a favourable histopathological response with no statistical significance due to the low number of cases. Conclusions: This study shows that single agent CET can lead to a marked and early decrease in tumor glucose uptake. Our findings suggest that there may be an association between the early decrease in FDG uptake during CET monotherapy, indicating a growth dependency of some tumors from the EGFR signal pathway. These preliminary observations require confirmation in a larger patient cohort. Clinical trial information: 2006-001097-24.

FDG-PET/CT of sarcoidosis and sarcoid reactions following antineoplastic treatment

Sarcoidosis or sarcoid reactions, which appear as FDG-avid lesions in oncologic patients, need to be differentiated from disseminated malignancies. We aimed to promote awareness of development of sarcoidosis or sarcoid reactions after antineoplastic therapy to avoid diagnostic errors with FDG-PET/CT findings and assess the utility of FDG-PET/CT for follow-up. We retrospectively reviewed radiological reports of FDG-PET/CT scans performed between January 2009 and December 2011. Among oncologic patients with more than 2 FDG-PET/CT scans, those with nearly symmetrical increases in FDG uptake in the hilar or mediastinal lymph nodes were identified, and those with known sarcoidosis, concurrent diagnoses of sarcoidosis with malignancy, or histopathologically proven malignancies were excluded. Then, only those cases were selected for which sarcoidosis or sarcoid reactions were diagnosed. Four of 376 oncologic cases met the criteria. At 9 months to 6 years after antineoplastic therapy, abnormal FDG uptakes were observed in the hilar, mediastinal, abdominal, pelvic, and inguinal nodes, and/or spleen and lung parenchyma with SUVmax up to 17.7. On the basis of these findings, 1 patient received anticancer chemotherapy because of tumor recurrence suspicion. A gradual decrease in FDG uptake was observed on subsequent PET/CT scans. Sarcoidosis or sarcoid reactions should be considered in differential diagnosis of oncologic patients who have developed FDG-avid lesions any time after antineoplastic therapy. FDG-PET/CT can be used for follow-up in nondiagnostic situations to detect decreases in FDG uptake due to presence of sarcoidal granulomas.

Early FDG/PET Scanning as a Pharmacodynamic Marker of Anti-EGFR Antibody Activity in Colorectal Cancer

Panitumumab is an anti-EGF receptor (EGFR) antibody approved for use in treatment of chemotherapy-refractory colorectal cancers lacking K-RAS mutations. Despite overall response rates approximating 10%, no marker predictive of clinical benefit has been identified. We describe a chemotherapy-refractory patient whose clinical condition necessitated rapid identification of an effective agent in whom we used (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomographic scanning 48 hours after an initial dose of panitumumab to document a pharmacodynamic response to the antibody. The initial 46% ± 2.7% drop in SUV(max) of four target lesions correlated with a partial response by Response Evaluation Criteria in Solid Tumors and a >90% drop in serum carcinoembryonic antigen at 8 weeks, indicating that an early decrease in FDG uptake may predict subsequent clinical benefit in response to anti-EGFR antibody therapy in colorectal cancer.

FDG-PET Parameters as Prognostic Factor in Esophageal Cancer Patients: A Review

Background. 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date concerning the potential prognostic value of FDG uptake in esophageal cancer patients, in terms of absolute pretreatment values and of decrease in FDG uptake during or after neoadjuvant therapy. Methods. A computer-aided search of the English language literature concerning esophageal cancer and standardized uptake values was performed. This search focused on clinical studies evaluating the prognostic value of FDG uptake as an absolute value or the decrease in FDG uptake and using overall mortality and/or disease-related mortality as an end point.