Positron Emission Tomography Standardized Uptake Research Articles

Circadian rhythms in older adults are associated with sleep quality, cognitive function, and ß‐amyloid burden: an accelerometry analysis of the Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial ‐ LEARNit

AbstractBackgroundSeveral studies demonstrate circadian rhythm disturbances in patients with Alzheimer’s disease. However, less is known about circadian rhythms in older adults with early mild cognitive impairment. Wrist‐worn accelerometers provide continuous, objective, high resolution quantification of 24‐hour rest activity rhythms. This study examines the relationship between circadian rhythms and sleep, cognition, and ß‐amyloid (Aß) burden.MethodThis study examines baseline data from the “Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial” (LEARNit). Sixty‐six older adults ages 55‐80 experiencing early cognitive changes wore a GENEActiv accelerometer for approximately 30 consecutive days. Accelerometer data was analyzed using the R package GGIR (version 2.8‐1), and circadian rhythm measures were extracted using the GGIR secondary package ActCR (version 0.3.0). Circadian rhythm variables include intradaily variability (fragmentation), interdaily stability (rhythm synchronization to light‐dark cycle), acrotime (peak activity time), and Midline Estimated Statistics of Rhythm or MESOR (mean activity level). Up‐MESOR and Down‐MESOR represent the timing of activity increasing above or decreasing below MESOR, respectively—lower values of each indicate a phase advance (shift towards morning), whereas higher values indicate a phase delay (shift towards evening). Sleep was assessed as mean sleep efficiency and Wake After Sleep Onset, or WASO (accumulated wakefulness after sleep onset). Cognitive tests include the Montreal Cognitive Assessment (MoCA) for global cognition and attention/processing speed (Digit Symbol Task). Aß burden was measured by positron emission tomography standard uptake value ratio for fifty‐six participants. Age‐adjusted linear regression models were used to test associations between circadian rhythms and sleep, cognition, and Aß.ResultParticipant characteristics are summarized in Table 1 and results are summarized in Figure 1. Intradaily variability (b = ‐0.095, p = 0.03) and interdaily stability (b = 0.34, p = 0.01) were both associated with mean sleep efficiency. Intradaily variability (b = 1.41, p<0.001) and interdaily stability (b = ‐4.45, p<0.001) were associated with WASO. Up‐MESOR was associated with MoCA total score (b = ‐0.41, p = 0.03). Up‐MESOR (b = ‐2.12, p = 0.006), Down‐MESOR (b = ‐1.99, p = 0.02), and acrotime (b = ‐4.20, p<0.001) were associated with Digit Symbol score. Down‐MESOR was significantly associated with Aß (b = ‐0.029, p = 0.02).ConclusionCircadian rhythm robustness is positively associated with better sleep quality. Participants with dynamic circadian rhythm phases demonstrated poorer cognition and higher Aß burden.

T Stage and Pretreatment Standardized Uptake Values Predict Tumor Recurrence With 5-Fraction SABR in Early-Stage Non-Small Cell Lung Cancer

PurposeFive-fraction stereotactic ablative radiotherapy (SABR) regimens are frequently used to treat centrally located early-stage non-small cell lung cancer or disease in the proximity of the chest wall as a means of optimizing tumor control and reducing treatment toxicity. However, increasing these SABR regimens to 5 fractions may reduce tumor control outcomes. We sought to identify the clinical parameters predictive of treatment failures with these 5-fraction courses. MethodsNinety patients with T1-2 non-small cell lung cancer were treated with 50 or 60 Gy in 5 fractions. Failure over time was modeled using cumulative incidences of local, regional, or distant failure, with death as a competing risk. Cox proportional hazards analysis for incidences of failure was performed to control for patient variables. ResultsOf 90 patients, 24 of 53 patients with T1 tumors and 19 of 37 patients with T2 tumors received 50 Gy SABR, and the other 47 patients received 60 Gy. Two-year overall survival and progression-free survival for the whole cohort were 75.8% and 59.3%, respectively. Total SABR dose (50 vs 60 Gy) did not influence survival nor failure rates at 2 and 5 years. Within 2 years of treatment, 7.8% of all patients developed local failure. For all patient and tumor characteristics evaluated, only T stage and pretreatment positron emission tomography standardized uptake values served as predictors of local, regional, and distant failure at 2 and 5 years posttreatment on univariate and multivariable analysis. ConclusionsFive-fraction SABR provides excellent in-field control. T2 and high fluorodeoxyglucose uptake tumors have increased failure rates, suggesting the potential need for adjuvant therapies, which are being assessed in randomized phase 3 trials.

Non-adjacent interlobar lymph node metastasis distant from small-sized peripheral non-small cell lung cancer.

The optimal extent of lymph node dissection (LND) during segmentectomy is unclear. During segmentectomy, it is more challenging to dissect the non-adjacent interlobar lymph node (non-aiLN) away from the primary tumor than to dissect the adjacent interlobar lymph node (aiLN), as injury to the preserved parenchyma and bronchus may occur. We examined whether dissection of non-aiLNs was required during intentional segmentectomy. This retrospective cohort study included 310 patients who underwent lobectomy and mediastinal LND for non-small cell lung cancer of ≤ 2cm at the Osaka International Cancer Institute during January 2006 to December 2015. We investigated LN metastasis distribution and evaluated metastases in non-aiLNs distant from the primary lesion. Six (1.9%) patients had iLN metastasis. Patients with iLN metastasis did not have primary lesions in the right upper lobe or left upper segment. Of the six patients with iLN metastasis, three had non-aiLN metastasis with a tumor diameter of ≥ 15mm, with high positron emission tomography standard uptake values (> 3.5). Two patients had multiple LN metastases, and one had solitary LN metastasis. Non-aiLN dissection may be unnecessary during segmentectomy of the right upper lobe or left upper segment; however, it should be considered during lower-lobe segmentectomy.

Evaluation of dose-dependent treatment effects after mid-trial dose escalation in biomarker, clinical, and cognitive outcomes for gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect. Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes. Both gantenerumab and solanezumab demonstrated dose-dependent treatment effects (significant for gantenerumab, non-significant for solanezumab) in their respective target amyloid biomarkers (Pittsburgh compound B positron emission tomography standardized uptake value ratio and cerebrospinal fluid amyloid beta 42), with gantenerumab demonstrating additional treatment effects in some downstream biomarkers. No dose-dependent treatment effects were observed in clinical or cognitive outcomes. Mid-trial dose escalation can be implemented as a remedy for an insufficient initial dose and can be more cost effective and less burdensome to participants than starting a new trial with higher doses, especially in rare diseases. We evaluated the dose-dependent treatment effect of two different amyloid-specific immunotherapies.Dose-dependent treatment effects were observed in some biomarkers.No dose-dependent treatment effects were observed in clinical/cognitive outcomes, potentially due to the fact that the modified study may not have been powered to detect such treatment effects in symptomatic subjects at a mild stage of disease exposed to high (or maximal) doses of medication for prolonged durations.

Discordance between positron emission tomography standard uptake value and proliferation index in mantle cell lymphoma: An initial communication.

Discordance between positron emission tomography standard uptake value and proliferation index in mantle cell lymphoma: An initial communication.

Ten-Year Experience in Implementing Single-Fraction Lung SBRT for Medically Inoperable Early-Stage Lung Cancer.

To review 10 years of using single-fraction lung stereotactic body radiation therapy (SF-SBRT) for medically inoperable peripheral early-stage lung cancer. An institutional review board-approved prospective lung SBRT data registry was surveyed until the end of December 2019 for all patients receiving SF-SBRT with minimum 6-month follow-up. Doses used were either 34 Gy or 30 Gy. Outcomes of interest included rates of local failure and overall survival (OS), as well as treatment-related toxicity graded per Common Terminology Criteria for Adverse Events version 3.0. A total of 229 patients met the study criteria. Patient characteristics included female sex (55%); median age, 74.6 years (range, 47-94); and median Karnofsky Performance Status 80 (range, 50-100). Tumor characteristics included median diameter, 1.6 cm (range, 0.7-4.1); median positron emission tomography standardized uptake value maximum 6.1 (range, 0.8-24.3); and 63.6% of patients biopsied. SF-SBRT dose was 34 Gy in 72.1% cases and 30 Gy in 27.9%, with patient and tumor characteristics balanced between cohorts. Overall median follow-up times for 30 Gy and 34 Gy were 36.7 and 17.2 months, respectively (P < .0001). At analysis, 55.9% patients were alive. Two (0.9%) patients developed grade 3 toxicities, and none had grade 4/5 toxicities. Grades 1 to 2 pneumonitis and chest wall toxicity were seen in 7% and 12.7% patients, respectively. Median overall survival was 44.1 months. Rates of 2-year local, nodal, and distant failure were 7.3%, 9.4%, and 12.2%, respectively. There were no significant differences in outcomes by dose. This is the largest institutional series to date reporting on SF-SBRT outcomes for medically inoperable peripheral early-stage lung cancer and the first to report on a decade's experience in implementing this schedule. Outcomes from this analysis are comparable to published results from 2 randomized trials and validate the use of this schedule in routine practice. In the absence of phase 3 trials, this study should encourage increased use of SF-SBRT for inoperable tumors.

Sleep quality and cortical amyloid-β deposition in postmenopausal women of the Kronos early estrogen prevention study.

Hormone therapy improves sleep in menopausal women and recent data suggest that transdermal 17β-estradiol may reduce the accumulation of cortical amyloid-β. However, how menopausal hormone therapies modify the associations of amyloid-β accumulation with sleep quality is not known. In this study, associations of sleep quality with cortical amyloid-β deposition and cognitive function were assessed in a subset of women who had participated in the Kronos early estrogen prevention study. It was a randomized, placebo-controlled trial in which recently menopausal women (age, 42-58; 5-36 months past menopause) were randomized to (1) oral conjugated equine estrogen (n = 19); (2) transdermal 17β-estradiol (tE2, n = 21); (3) placebo pills and patch (n = 32) for 4 years. Global sleep quality score was calculated using Pittsburgh sleep quality index, cortical amyloid-β deposition was measured with Pittsburgh compound-B positron emission tomography standard uptake value ratio and cognitive function was assessed in four cognitive domains 3 years after completion of trial treatments. Lower global sleep quality score (i.e., better sleep quality) correlated with lower cortical Pittsburgh compound-B standard uptake value ratio only in the tE2 group (r = 0.45, P = 0.047). Better global sleep quality also correlated with higher visual attention and executive function scores in the tE2 group (r = -0.54, P = 0.02) and in the oral conjugated equine estrogen group (r = -0.65, P = 0.005). Menopausal hormone therapies may influence the effects of sleep on cognitive function, specifically, visual attention and executive function. There also appears to be a complex relationship between sleep, menopausal hormone therapies, cortical amyloid-β accumulation and cognitive function, and tE2 formulation may modify the relationship between sleep and amyloid-β accumulation.

Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-β–negative cognitively normal individuals

We examined whether mesial temporal (Me) tau relates to cognitive performance in 47 amyloid-β (Aβ)-negative, cognitively normal older adults (>60 years old). Me-tau was measured using [18F]flortaucipir–positron emission tomography standardized uptake value ratio. The effect of continuous and categorical (stratified at standardized uptake value ratio = 1.2 [21% Me-positive]) Me-tau on cognition (mini-mental state examination, pre-Alzheimer's cognitive composite, a memory composite, and a nonmemory composite score) was examined using general linear models, and associations between Me-tau and [18F]flortaucipir signal in the neocortex were assessed using voxelwise regressions (continuous) and voxelwise contrasts (categorical). In addition, we assessed the effect of age and Aβ burden on Me-tau. Both continuous and categorical Me-tau was associated with worse cognitive performance across all tests and with higher lateral temporal and parietal [18F]flortaucipir signal. Furthermore, we observed a marginal association between Me-tau and age, whereas there was no association with Aβ burden. Our findings indicate that Me-tau in Aβ-negative cognitively normal individuals, which is likely age-related (i.e., primary age-related tauopathy), might not be as benign as commonly thought.

The role of age on tau PET uptake and gray matter atrophy in atypical Alzheimer's disease

IntroductionLittle is known about the role of age on neurodegeneration and protein deposition in atypical variants of Alzheimer's disease (AD). MethodsRegional tau and β-amyloid positron emission tomography standard uptake value ratios and gray matter volumes were calculated in a cohort of 42 participants with atypical AD. The relationship between regional metrics and age was modeled using a Bayesian hierarchical linear model. ResultsAge was strongly associated with tau uptake across all cortical regions, particularly parietal, with greater uptake in younger participants. Younger age was associated with smaller parietal and lateral temporal volumes. Regional β-amyloid differed little by age. Age showed a stronger association with tau than volume and β-amyloid in all cortical regions. Age was not associated with cognitive performance. DiscussionAge is an important determinant of severity of cortical tau uptake in atypical AD, with young participants more likely to show widespread and severe cortical tau uptake.

Amyloid beta-positive subjects exhibit longitudinal network-specific reductions in spontaneous brain activity.

Amyloid beta (Aβ) deposition and cognitive decline are key features of Alzheimer's disease. The relationship between Aβ status and changes in neuronal function over time, however, remains unclear. We evaluated the effect of baseline Aβ status on reference region spontaneous brain activity (SBA-rr) using resting-state functional magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in patients with mild cognitive impairment. Patients (N= 62, [43 Aβ-positive]) from the Alzheimer's Disease Neuroimaging Initiative were divided into Aβ-positive and Aβ-negative groups via prespecified cerebrospinal fluid Aβ42 or 18F-florbetapir positron emission tomography standardized uptake value ratio cutoffs measured at baseline. We analyzed interaction of biomarker-confirmed Aβ status with SBA-rr change over a 2-year period using mixed-effects modeling. SBA-rr differences between Aβ-positive and Aβ-negative subjects increased significantly over time within subsystems of the default and visual networks. Changes exhibit an interaction with memory performance over time but were independent of glucose metabolism. Results reinforce the value of resting-state functional magnetic resonance imaging in evaluating Alzheimer''s disease progression and suggest spontaneous neuronal activity changes are concomitant with cognitive decline.

A Competing Risk Model of First Failure Site after Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

The aim of the study was to build a model of first failure site- and lesion-specific failure probability after definitive chemoradiotherapy for inoperable NSCLC. We retrospectively analyzed 251 patients receiving definitive chemoradiotherapy for NSCLC at a single institution between 2009 and 2015. All patients were scanned by fludeoxyglucose positron emission tomography/computed tomography for radiotherapy planning. Clinical patient data and fludeoxyglucose positron emission tomography standardized uptake values from primary tumor and nodal lesions were analyzed by using multivariate cause-specific Cox regression. In patients experiencing locoregional failure, multivariable logistic regression was applied to assess risk of each lesion being the first site of failure. The two models were used in combination to predict probability of lesion failure accounting for competing events. Adenocarcinoma had a lower hazard ratio (HR) of locoregional failure than squamous cell carcinoma (HR=0.45, 95% confidence interval [CI]: 0.26-0.76, p=0.003). Distant failures were more common in the adenocarcinoma group (HR= 2.21, 95% CI: 1.41-3.48, p<0.001). Multivariable logistic regression of individual lesions at the time of first failure showed that primary tumors were more likely to fail than lymph nodes (OR= 12.8, 95% CI: 5.10-32.17, p < 0.001). Increasing peak standardized uptake value was significantly associated with lesion failure (OR= 1.26 per unit increase, 95% CI: 1.12-1.40, p < 0.001). The electronic model is available at http://bit.ly/LungModelFDG. We developed a failure site-specific competing risk model based on patient- and lesion-level characteristics. Failure patterns differed between adenocarcinoma and squamous cell carcinoma, illustrating the limitation of aggregating them into NSCLC. Failure site-specific models add complementary information to conventional prognostic models.

Measuring temporal stability of positron emission tomography standardized uptake value bias using long-lived sources in a multicenter network.

Positron emission tomography (PET) is a quantitative imaging modality, but the computation of standardized uptake values (SUVs) requires several instruments to be correctly calibrated. Variability in the calibration process may lead to unreliable quantitation. Sealed source kits containing traceable amounts of [Formula: see text] were used to measure signal stability for 19 PET scanners at nine hospitals in the National Cancer Institute's Quantitative Imaging Network. Repeated measurements of the sources were performed on PET scanners and in dose calibrators. The measured scanner and dose calibrator signal biases were used to compute the bias in SUVs at multiple time points for each site over a 14-month period. Estimation of absolute SUV accuracy was confounded by bias from the solid phantoms' physical properties. On average, the intrascanner coefficient of variation for SUV measurements was 3.5%. Over the entire length of the study, single-scanner SUV values varied over a range of 11%. Dose calibrator bias was not correlated with scanner bias. Calibration factors from the image metadata were nearly as variable as scanner signal, and were correlated with signal for many scanners. SUVs often showed low intrascanner variability between successive measurements but were also prone to shifts in apparent bias, possibly in part due to scanner recalibrations that are part of regular scanner quality control. Biases of key factors in the computation of SUVs were not correlated and their temporal variations did not cancel out of the computation. Long-lived sources and image metadata may provide a check on the recalibration process.

Tumor Control and Toxicity for Common Stereotactic Body Radiation Therapy Dose-Fractionation Regimens in Stage I Non-Small Cell Lung Cancer

To examine the impact of stereotactic body radiation therapy (SBRT) dose on outcomes in early-stage non-small cell lung cancer in a large single-institution series. We reviewed 600 patients treated from 2003 to 2012 for early-stage non-small cell lung cancer. The SBRT dose was at physician discretion on the basis of tumor size and location. Peripheral tumors were treated to 60Gy in 3 fractions (homogeneous planning), 48-50Gy in 4-5 fractions, or 30-34Gy in 1 fraction. Central tumors were treated to 50Gy in 5 fractions, 60Gy in 8 fractions, or 50Gy in 10 fractions. Patient, tumor, and treatment factors were assessed for their impact on patterns of failure, toxicity, and survival. An SBRT dose of 54-60Gy in 3 fractions was associated with a statistically significant lower rate of local failure (LF) (4.3% at 2years) compared with 30-34Gy in 1 fraction (21%), 48-50Gy in 4-5 fractions (15.5%), and 50-60Gy in 8-10 fractions (13.3%). Lower pre-SBRT hemoglobin and higher positron emission tomography standardized uptake value were also associated with LF. Nodal failure, distant failure, and overall survival were similar between fractionation groups. Pulmonary toxicity (crude rate, any grade) was slightly higher for 3 fractions (5.0%) compared with 1 (3.2%) or 4-5 fractions (3.8%). Chest wall toxicity was also higher for 3 (23.7%) compared with 1 (8.6%) or 4-5 (7.7%) fraction regimens. Although higher biologically equivalent dose SBRT (150-180 Gy10) may be associated with slightly lower LF, it was also associated with mildly increased toxicity and no difference in other patterns of failure or overall survival.

Biochemically-defined pools of amyloid-β in sporadic Alzheimer's disease: correlation with amyloid PET.

We fractionated frontal cortical grey matter from human Alzheimer's disease and control subjects into four biochemically defined pools that represent four distinct compartments: soluble/cytosolic, peripheral membrane/vesicular cargo, integral lipid/membranous pools and aggregated/insoluble debris. Most of the readily extractable amyloid-β remains associated with a lipid/membranous compartment. There is an exchange of amyloid-β between the biochemical pools that was lost for the amyloid-β42 species in Alzheimer's disease, consistent with the peptide being irreversibly trapped in extracellular deposits. The quantitative amyloid-β data, combined with magnetic resonance imaging volumetric analysis of the amount of cortical grey matter in brain, allowed us to estimate the total mass of amyloid-β in Alzheimer's disease (6.5 mg) and control (1.7 mg) brains. The threshold positron emission tomography standard uptake value ratio of 1.4 equates to 5.0 μg amyloid-β/g of grey matter and the mean Alzheimer's disease dementia standard uptake value ratio level of 2.3 equates to 11.20 μg amyloid-β/g of grey matter. It takes 19 years to accumulate amyloid from the threshold positron emission tomography standard uptake value ratio to the mean value observed for Alzheimer's disease dementia. This accumulation time window combined with the difference of 4.8 mg of amyloid-β between Alzheimer's disease and control brain allows for a first approximation of amyloid-β accumulation of 28 ng/h. This equates to an estimated 2-5% of the total amyloid-β production being deposited as insoluble plaques. Understanding these rates of amyloid-β accumulation allows for a more quantitative approach in targeting the failure of amyloid-β clearance in sporadic Alzheimer's disease.

A Histologic Basis for the Efficacy of SBRT to the lung

PurposeStereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early-stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established. MethodsWe analyzed 740 patients with early-stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression. ResultsOverall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3-year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7–25.1), 8.7% (95% CI: 4.6–12.8), and 4.1% (95% CI: 0–9.6), respectively. ConclusionOur results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.

Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non-small cell lung cancer patients with KRAS-activated tumors.

The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a Ras-activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents. This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic/recurrent KRAS-mutated or epidermal growth factor receptor (EGFR)-mutated/amplified non-small cell lung cancer. Thirty-seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF-V600E mutations. In total, 242 cycles (median, 4; range, 1-47) were completed. The initial doses were area under the curve (AUC) 6 mg/mL/min for carboplatin, 200 mg/m(2) for paclitaxel on day 1, and 3 × 10(10) 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21-day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175 mg/m(2) for paclitaxel and AUC 5 mg/mL/min for carboplatin. Toxicities included fatigue, diarrhea, nausea/vomiting, neutropenia, arthralgia/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1-sided lower confidence interval, 21%). Four SD patients had >40% positron emission tomography standardized uptake value reductions. The median progression-free survival, median overall survival, and 12-month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow-up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months. Reolysin in combination with paclitaxel and carboplatin was well tolerated. The observed response rate suggests a benefit of the reovirus for chemotherapy. A follow-up randomized study is recommended. The proportion of patients surviving longer than 2 years (30%) suggests a second/third-line treatment effect or possibly the triggering of an immune response after tumor reovirus infiltration.

18F-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography Standard Uptake Value Ratio as an Indicator of Cervical Cancer Chemoradiation Therapeutic Response

A ratio of 3 months of posttherapy to pretherapy 2-[F]fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography (F-FDG PET/CT) standard uptake values (SUVs) predicts progression-free survival after chemoradiation in patients with stages IB2 to IVA cervical cancer. This retrospective review included 51 patients who received treatments of daily pelvic radiation and once-weekly cisplatin chemotherapy followed by brachytherapy. Posttherapy confirmatory surgical or cytologic pathology was done a median of 7 days after 3-month F-FDG PET/CT. All 51 patients receiving chemoradiation achieved at least a partial metabolic response (ie, >25% decrease in F-FDG PET/CT SUV) in the expected region of the cervix. A ratio of less than 0.33 for posttherapy to pretherapy F-FDG PET/CT SUVs of the expected area of the cervix was associated with a 35% improvement in 6-month progression-free survival. In patients with cervical cancer, the 3-month posttherapy F-FDG PET/CT value is an indicator of therapeutic response to chemoradiation and needs further validation in clinical trials.

Correlation of [18F]‐2‐fluoro‐deoxy‐D‐glucose positron emission tomography standard uptake values with the cellular composition of stage I nonsmall cell lung cancer

The aim of the current study was to determine whether the [18F]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) standardized uptake value (SUV) in patients with a new diagnosis of stage I lung cancer correlates with a specific cellular component in the primary tumor. This study was Health Insurance Portability and Accountability Act compliant and approved by our Institutional Review Board with a waiver of informed consent. Forty patients with stage I nonsmall cell lung cancer (NSCLC) who underwent FDG-PET imaging at the time of diagnosis followed by surgical resection were retrospectively identified. Histologic sections of the primary tumor were reviewed by a pathologist without any clinical data and scored according to the percentage of each cellular component (tumor cells, normal stroma, inflammatory cells, necrosis, fibrosis, and other). Each component was compared with maximal (SUV(max)) and mean (SUV(mean)) SUVs using Pearson correlation coefficient analysis. The mean SUV(max) and SUV(mean) values for 40 stage I NSCLC tumors were 8.8 and 5.4, respectively. The mean histologic composition of tumor specimens in order of frequency was as follows: tumor cells (38.9%), fibrosis (30.8%), inflammatory cells (14.8%), normal stroma (5.2%), necrosis (5.8%), and other components (4.5%); however, there was considerable variation noted among individual tumors. There was no statistically significant correlation between SUV(max) (r = .19; P = .24) or SUV(mean) (r = .017; P = .29) and the proportion of tumor cells in the tumor mass or any other cellular components. The cellular composition of stage I NSCLC appears to be highly variable, with no correlation noted between a specific tumor cellular component and FDG activity.

Predictive Value of Initial PET-SUVmax in Patients with Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma

We have previously shown that in early clinical stage esophageal adenocarcinoma, a positron emission tomography standardized uptake values (PET SUVmax) of <4.5 is associated with earlier pathologic stage and predicts better survival. In this study, we analyze the impact of the pretreatment PET SUVmax in patients with locally advanced esophageal adenocarcinoma who undergo preoperative chemoradiotherapy. We performed a retrospective analysis, selecting patients with adenocarcinoma of the esophagus who had a pretreatment PET scan and who received chemoradiotherapy before esophagectomy. Data recorded included demographics, PET SUVmax, treatment details, pathologic details, and survival data. Comparison of categorical variables was done by chi analysis, continuous variables by t test, survival analysis by the Kaplan-Meier method, and comparisons of survival using the log-rank test. Between January 1996 and September 2007, 189 patients were appropriate for this analysis. The initial PET SUVmax was <4.5 in 28 patients and >or=4.5 in 161 patients. The two groups were similar with regards to demographics and treatment details. Patients in the low SUV group were less likely to show evidence of treatment response after chemoradiotherapy, including a higher likelihood of residual nodal disease and a lower likelihood of a pathologic complete response and estimated treatment response. However, both groups had similar survival. Although the initial PET SUVmax does not predict survival in patients with locally advanced esophageal adenocarcinoma who receive preoperative chemoradiotherapy, patients with a high initial SUVmax respond better to preoperative therapy. These results can be used to better select esophageal cancer patients for combined modality treatment.

Preoperative [18F]-fluorodeoxyglucose positron emission tomography standardized uptake value of neck lymph nodes may aid in selecting patients with oral cavity squamous cell carcinoma for salvage therapy after relapse

Relapse of tumours in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a dismal outcome. In this prospective study, we sought to investigate the clinical significance of the preoperative maximal standardized uptake value (SUVmax) at the neck lymph nodes in selecting patients with OSCC for salvage therapy after relapse. Between 2002 and 2007, 108 patients with early relapse of OSCC (n=75) or late relapse of OSCC (n=33) were identified. Salvage therapy was performed in 47 patients. All patients underwent 2-deoxy-2[(18)F]-fluoro-D: -glucose positron emission tomography during the 2 weeks before surgery and neck dissection. All patients were followed for 12 months or more after surgery or until death. The optimal cut-off value for the neck lymph node SUVmax (SUVnodal-max) was selected according to the 5-year disease-specific survival (DSS) rate. Independent risk factors were identified by Cox regression analysis. The mean follow-up for all patients was 20.3 months (41.1 months for surviving patients). In the early relapse group, several prognostic factors were identified in univariate and multivariate analyses, including a SUVnodal-max value of >or=4.2. A scoring system based on univariate analysis was formulated. Patients with a score of 0 had a better 5-year DSS than those with scores of 1 or higher (58% vs. 5%, p=0.0003). In patients with late relapse, a SUVnodal-max value of >or=4.2 had the highest prognostic value for predicting the 5-year DSS (45% vs. 0%, p=0.0005). Among patients with relapsed OSCC, the SUVnodal-max value may aid in selecting patients for salvage therapy.