Percentage Change In SUVmax Research Articles

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n=163) and follow-up FDG-PET/CT at 3 or 6 months (n=71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P=.006), >12.3 for PFS (aHR, 2.80, P=.011), and >12.6 for OS (aHR, 3.00, P=.003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P=.018), and 53% at 6 months (aHR, 0.12, P=.046) were associated with improved local failure-free survival. Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

Tumor Control and Survival Outcomes Based on Maximum Standardized Uptake Value on FDG-PET/CT in T1-2 NSCLC Treated With SBRT

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is standard of care in medically inoperable early-stage non-small cell lung cancer (NSCLC). Assessment of maximum standardized uptake value (SUVmax) on FDG-PET/CT before and after SBRT may stratify tumor control and survival outcomes. <h3>Materials/Methods</h3> Retrospective chart review identified patients with T1-2N0M0 NSCLC who were only treated with SBRT between 2012 and 2019. Pretreatment SUVmax and percent change in SUVmax at 3 and 6 months following SBRT were assessed as independent predictors of local control (LC), regional failure-free survival (RFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS). Receiver operator characteristic (ROC) analysis yielded optimal cut points for comparison. Survival analyses were performed with Kaplan-Meier estimates with log rank testing, and Cox proportional hazards models including age, sex, T stage, histology, and performance status. <h3>Results</h3> 71 (43.6%) out of 163 patients underwent repeat PET/CT within 6 months of SBRT completion. Median follow-up was 19 months (range 1 – 94 months). For the whole cohort, 1-year and 2-year LC, PFS, and OS were 95.0% and 80.3%, 75.9% and 47.7%, and 87.1% and 67.0%, respectively. For DFFS, pretreatment SUVmax greater than 4 had an aHR of 3.33 (95% CI 1.42 – 7.84, <i>P</i> = 0.006). Pre-SBRT SUVmax over 12.3 had an aHR of 2.80 (95% CI 1.3 – 6.2, <i>P</i> = 0.011) for PFS, and a cut point of 12.6 had an aHR of 3.00 (95% CI 1.6 – 5.8, <i>P</i> = 0.003) for OS. Pretreatment SUVmax did not significantly predict LC or RFFS. At 3 months following SBRT, an SUVmax decrease of at least 45% was associated with improved LC (aHR = 0.15, 95% CI 0.02 – 0.91, <i>P</i> = 0.018). A 6-month SUVmax decrease of more than 53% was associated with better LC (<i>P</i> = 0.038), and a decrease over 11% was associated with improved RFFS (aHR = 0.12, 95% CI 0.02 – 0.96, <i>P</i> = 0.046). Change in SUVmax was not significantly associated with DFFS, PFS, or OS at either time point. No factors other than performance status for PFS and OS were significant. <h3>Conclusion</h3> At 3 and 6 months following SBRT, cut points for percentage change in SUVmax can stratify risk of local recurrence and possibly regional recurrence. Pretreatment SUVmax cutoffs can predict distant failure, progression-free survival, and overall survival in early-stage NSCLC.

Peptide Receptor Radionuclide Therapy of Late-Stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE.

This study aimed to evaluate the safety and efficacy of multiple cycles of 177Lu-DOTA-Evans blue (EB)-TATE peptide receptor radionuclide therapy (PRRT) at escalating doses in neuroendocrine tumors (NETs). Methods: Thirty-two NET patients were randomly divided into 3 groups and treated with escalating doses. Group A received 1.17 ± 0.09 GBq/cycle; group B, 1.89 ± 0.53 GBq/cycle; and group C, 3.97 ± 0.84 GBq/cycle. The treatment was planned for up to 3 cycles. Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Treatment response was evaluated according to the European Organisation for Research and Treatment of Cancer criteria and modified PERCIST. Results: Administration of PRRT was well tolerated, without life-threatening adverse events (CTCAE grade 4). CTCAE grade 3 hematotoxicity was recorded in 1 patient (16.6%) in group B (thrombocytopenia) and 3 patients (21.4%) in group C (thrombocytopenia in 3, anemia in 1). CTCAE grade 3 hepatotoxicity (elevated aspartate aminotransferase) was recorded in 1 patient in group A (8.3%) and 1 patient in group C (7.1%). No nephrotoxicity was observed. According to the criteria of the European Organisation for Research and Treatment of Cancer, the overall disease response rates were similar in groups A, B, and C (50.0%, 50.0%, and 42.9%, respectively), and the overall disease control rates were higher in groups B (83.3%) and C (71.5%) than in group A (66.7%). According to modified PERCIST, a lower disease response rate but a similar disease control rate were found. When a comparable baseline SUVmax ranging from 15 to 40 was selected, the percentage change in SUVmax increased slightly in group A (2.1% ± 40.8%) but decreased significantly in groups B and C (-38.7% ± 10.0% and -14.7% ± 20.0%, respectively) after the first PRRT (P = 0.001) and decreased in all 3 groups after the third PRRT (groups A, B, and C: -6.9% ± 42.3%, -49.2% ± 30.9%, -11.9% ± 37.9%, respectively; P = 0.044). Conclusion: Dose escalations of up to 3.97 GBq/cycle seem to be well tolerated for 177Lu-DOTA-EB-TATE. 177Lu-DOTA-EB-TATE doses of 1.89 and 3.97 GBq/cycle were effective in tumor control and more effective than 1.17 GBq/cycle.

Impact of free-breathing CT on quantitative measurements of static and quiescent period-gated PET Images

Measurements of standardized uptake values (SUV) can vary due to many causes, including respiratory motion. Various methodologies have been introduced to correct for motion in PET, with quiescent-period-gated (QPG) PET being the most popular approach. QPG has been shown to improve PET image quantification compared to static-whole-body (SWB) PET. However, to achieve this improvement, QPG PET requires CT attenuation correction data that matches the QPG PET data. In this paper we investigated the effect of using free-breathing CT for attenuation correction of QPG PET on SUVmax and SUVpeak and compared the results to those of SWB PET. 34 lesions in 27 patients were included. All patients were injected with F-18 FDG. 4D-CT datasets representing all possible phases of respiration that could result from a free-breathing CT were acquired. The 4D-CT datasets were used for attenuation correction of the QPG and SWB PET data. Percentage change in the SUVmax and SUVpeak range was calculated for the reconstructions and compared between QPG and SWB PET. The mean percentage change in the lesion SUVmax and SUVpeak ranges were 19.1% (p = 0.0178) and 25.2% (p = 0.0002) higher for QPG compared to SWB, respectively. The maximum percent change in SUVmax and SUVpeak ranges were 58.5% and 59.0% for QPG, respectively compared to 46.1% and 45.3% for SWB, respectively. The highest SUVmax and SUVpeak measurements corresponded to the CT phase that matched the QPG phase. Utilizing free-breathing CT for attenuation correction can lead to large changes in quantification due to misalignment with PET data. This misalignment has a large quantitative impact on QPG PET as compared to SWB PET. When interpreting quantitative changes in lesions, it is critical to consider the influences of free-breathing CT-based attenuation correction.

Value of FDG-PET/CT for treatment response in tuberculosis: a systematic review and meta-analysis

Tuberculosis (TB) is an infectious disease with a high global incidence and substantial disease burden. Monitoring disease activity and evaluating treatment response with conventional methods such as culture or chest x-ray is time-consuming and non-specific. Active TB lesions are typically highly FDG-avid and may be assessed on whole-body 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). We hypothesized that FDG-PET or FDG-PET/CT is useful for evaluation of treatment response and outcome in TB-infected patients undergoing anti-tuberculosis therapy (ATT). PubMed and Embase databases were searched and original studies with humans infected with Mycobacterium tuberculosis receiving ATT and a minimum of one FDGPET/CT or FDG-PET scan were included. Percentage change in maximum standardized uptake value (SUVmax) from baseline was assessed with a fixed-effects model using the inverse variance method supplemented by a Forest Plot. Publication bias and heterogeneity between studies was assessed with a Funnel plot and the I squared statistic, respectively. A total of 2048 articles were identified and nine were included in the review. Four studies were included in the meta-analysis. The estimated overall percentage change in SUVmax was − 54.38% (95% confidence interval − 57.81 to − 50.96) and the heterogeneity between studies was high (I 2 = 90.1%). Study design, protocol, sample size and ATT varied between studies. Despite high heterogeneity there was a trend towards the usefulness of FDG-PET or FDG-PET/CT for evaluation of ATT response. Impending research is needed to further clarify the predictive value of FDG-PET/CT in tuberculous disease.

Uptake of Radium-223 Dichloride and Early [18F]NaF PET Response Are Driven by Baseline [18F]NaF Parameters: a Pilot Study in Castration-Resistant Prostate Cancer Patients.

The purpose of this study is to identify predictive factors on baseline [18F]NaF positron emission tomography (PET)/computed tomography (CT) of early response to radium-223 dichloride after 3 cycles of treatment in metastatic castration-resistant prostate cancer patients. Analysis of 152 metastases was performed in six consecutive patients who underwent [18F]NaF PET/CT at baseline and for early monitoring after 3 cycles of radium-223 dichloride. All metastases depicted on whole-body [18F]NaF PET/CT were contoured and CT (density in Hounsfield units, sclerotic, mixed, or lytic appearance) as well as [18F]NaF [maximum standardized uptake value (SUVmax), SUVmean, and lesion volume (V18F-NaF)] patterns were recorded. Tumor response was defined as percentage change in SUVmax and SUVmean between baseline and post-treatment PET. Bone lesions were defined as stable, responsive, or progressive, according to thresholds derived from a recent multicentre test-retest study in [18F]NaF PET/CT. Total [18F]NaF uptake in metastases, defined as MATV×SUVmean, was correlated to uptake of radium-223 on biodistribution scintigraphy performed 7days after the first cycle of treatment. Among metastases, 116 involved the axial skeleton and 36 the appendicular skeleton. Lesions were sclerotic in 126 cases and mixed in 26 cases. No lytic lesion was depicted. ROC analysis showed that SUVmax and SUVmean were better predictors of lesion response than V18F-NaF and density on CT (P<0.0001 and P=0.001, respectively). SUVmax and SUVmean were predictors of individual tumor response in separate multivariate models (P=0.01 and P=0.02, respectively). CT pattern (mixed versus sclerotic) and lesion density were independent predictors only when assessing response with delta SUVmax (P=0.002 and 0.007, respectively). A good correlation between total [18F]NaF uptake within metastases and their relative radium-223 uptake assessed by two observers 7days after treatment (r=0.72 and 0.77, P<0.0001) was found. SUVmax and SUVmean on baseline [18F]NaF PET/CT are independent predictors of bone lesions' response to 3 cycles of radium-223 dichloride, supporting the use of NaF to select patients more likely to respond to treatment.

Quantitation of Cancer Treatment Response by 18F-FDG PET/CT: Multicenter Assessment of Measurement Variability

The aim of this study was to assess the interobserver variability of quantitative 18F-FDG PET/CT parameters used in assessments of treatment response across multiple sites and readers. Methods: Paired pre- and posttreatment 18F-FDG PET/CT images of 30 oncologic patients were distributed to 22 readers across 15 U.S. and international sites. One reader was aware of the full medical history (readreference) of the patients, whereas the 21 other readers were unaware. The readers selected the single hottest tumor from each study, and made SUV measurements from this target lesion and the liver. Descriptive statistics, percentage changes in the measurements, and their agreements were obtained. Results: The intraclass correlation coefficient for the percentage change in SUVmax (%ΔSUVmax) of the hottest tumor was 0.894 (95% confidence interval [CI], 0.813-0.941), and the individual equivalence coefficient was 1.931 (95% CI, 0.568-6.449) when all reads were included (n = 638). When only the measurements that selected the same target tumor as the readreference (n = 486) were included, the intraclass correlation coefficient for the %ΔSUVmax was 0.944 (95% CI, 0.841-0.989), and the individual equivalence coefficient was -0.688 (95% CI, -1.810 to -0.092). The absolute change in SUVmean of liver corrected for lean body mass showed upper and lower limits of agreement (average bias ± 2 SDs) of 0.13 and -0.13 g/mL. Conclusion: The quantitative tumor SUV changes measured across multiple sites and readers show a high correlation. Selection of the same tumor target among readers further increased the degree of correlation.

Dual time-point 18F-FDG PET/CT to assess response to radiofrequency ablation of lung metastases

AimTo establish the usefulness of dual time-point PET/CT imaging in determining the response to radiofrequency ablation (RFA) of solitary lung metastases from gastrointestinal cancer. Materials and methodsThis prospective study included 18 cases (3 female, 15 male, mean age 71±15 yrs) with solitary lung metastases from malignant digestive tract tumors candidates for RFA. PET/CT images 1h after injection of 4.07MBq/kg of 18F-FDG (standard images) were performed at baseline, 1 month, and 3 months after RFA. PET/CT images 2h after injection centered in the thorax at 1 month after RFA were also performed (delayed images). A retention index (RI) of dual time-point images was calculated as follows: RI=(SUVmax delayed image−SUVmax standard image/SUVmax standard image)*100. Pathological confirmation of residual tumor by histology of the treated lesion was considered as local recurrence. A negative imaging follow-up was considered as complete response. ResultsLocal recurrence was found in 6/18 lesions, and complete response in the remaining 12. The mean percentage change in SUVmax at 1 month and at 3 months showed a sensitivity and specificity for PET/CT of 50% and 33%, and 67% and 92%, respectively. The RI at 1 month after RFA showed a sensitivity and specificity of 83% and 92%, respectively. ConclusionsDual time point PET/CT can predict the outcome at one month after RFA in lung metastases from digestive tract cancers. The RI can be used to indicate the need for further procedures to rule out persistent tumor due to incomplete RFA.

Dual time-point (18)F-FDG PET/CT to assess response to radiofrequency ablation of lung metastases.

To establish the usefulness of dual time-point PET/CT imaging in determining the response to radiofrequency ablation (RFA) of solitary lung metastases from gastrointestinal cancer. This prospective study included 18 cases (3 female, 15 male, mean age 71±15 yrs) with solitary lung metastases from malignant digestive tract tumors candidates for RFA. PET/CT images 1h after injection of 4.07MBq/kg of (18)F-FDG (standard images) were performed at baseline, 1 month, and 3 months after RFA. PET/CT images 2h after injection centered in the thorax at 1 month after RFA were also performed (delayed images). A retention index (RI) of dual time-point images was calculated as follows: RI=(SUVmax delayed image-SUVmax standard image/SUVmax standard image)*100. Pathological confirmation of residual tumor by histology of the treated lesion was considered as local recurrence. A negative imaging follow-up was considered as complete response. Local recurrence was found in 6/18 lesions, and complete response in the remaining 12. The mean percentage change in SUVmax at 1 month and at 3 months showed a sensitivity and specificity for PET/CT of 50% and 33%, and 67% and 92%, respectively. The RI at 1 month after RFA showed a sensitivity and specificity of 83% and 92%, respectively. Dual time point PET/CT can predict the outcome at one month after RFA in lung metastases from digestive tract cancers. The RI can be used to indicate the need for further procedures to rule out persistent tumor due to incomplete RFA.

Use of 18F-FDG-PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Children With Wilms Tumor

The aim of this study was to evaluate the predictive value of fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (F-FDG-PET-CT) in the assessment of histologic response to neoadjuvant chemotherapy in children with Wilms tumors (WTs). We prospectively registered 12 patients with WTs who were treated with 2 cycles of neoadjuvant chemotherapy and surgery. All patients underwent sequential F-FDG-PET-CT before (PET-CT1) and after (PET-CT2) neoadjuvant chemotherapy. Maximum standardized uptake value (SUVmax) was measured on PET-CT1 (SUV1) and PET-CT2 (SUV2). The percentage change in SUVmax (SUVmax reduction) was calculated. After surgery the effects of neoadjuvant chemotherapy were graded histopathologically: ≥90% necrosis indicated a good response and <90% necrosis was considered a poor response. The correlation between SUVmax reduction and histologic response was estimated using the Spearman correlation coefficient. Among the 12 patients who underwent PET-CT before and after chemotherapy, SUVmax reduction was significantly different between the good response group and the poor response group (P=0.035). A significant, in terms of P value, correlation was found between pathologic response and SUVmax reduction (r=0.700; 95% confidence interval, 0.060-0.935; P=0.011). A threshold of 66% reduction in SUVmax was identified, with which partition, there were 8 good histologic responders (≥66% decrease in SUVmax) and 4 poor responders. The histologic complete response rate of the good responders was 87.5%, whereas that of poor responders was 0%. SUV1≥7 and SUV2≥2.4 were both considered to be with high risk of recurrence. In patients with SUV1≥7, 4/5 cases relapsed and 4/6 patients with SUV2≥2.4 relapsed. As there seems to be a good correlation of changes in SUVmax and histologic response, PET-CT has the potential of predicting the response to neoadjuvant chemotherapy in children with WT. SUV1 and SUV2 by themselves might be a good prognosticator of the clinical outcome of WT pediatric patients treated with International Society of Pediatric Oncology protocols, although the reduction rate of SUVmax is much less powerful for prognosis.

Tumor SUVmax Normalized to Liver Uptake on (18)F-FDG PET/CT Predicts the Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

This study investigates the feasibility of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) to predict the pCR (pathologic complete response) rate after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer. A total of 88 patients with locally advanced rectal cancer were retrospectively analyzed. All patients were treated with NCRT, followed by radical surgery, and (18)F-FDG PET/CT was performed before and after NCRT. For a semiquantitative assessment, a volume of interest was drawn, including the whole tumor region, and the maximum SUV (SUVmax), SUVmax normalized to liver uptake (SLR), SUVmax normalized to blood pool uptake (SBR), the metabolic tumor volume at SUV 2.0 (MTV[2.0]), SUV 2.5 (MTV[2.5]), and SUV 3.0 (MTV[3.0]) were measured. In addition, their percentage changes after NCRT were assessed. The pCR was verified through a histologic examination of postsurgical specimens. A receiver operating characteristic curve analysis was conducted to predict the pCR by using these PET parameters. The pCR was predicted in 17 patients (19%). The values of the area under the curve (AUC) for predicting the pCR were 0.774 for SUVmax after NCRT, 0.826 for SLR after NCRT, 0.815 for SBR after NCRT, 0.724 for MTV(2.5) after NCRT, 0.729 for the percentage change in SUVmax, 0.700 for the percentage change in SLR, and 0.749 for the percentage change in MTV (2.5). Among these PET parameters, SLR after NCRT showed the highest AUC value. The optimal criterion, sensitivity, specificity, and accuracy of SLR after NCRT for predicting the pCR were ≤1.41, 88%, 65%, and 68%, respectively. F-FDG PET was found to be useful for predicting the pCR after NCRT in patients with locally advanced rectal cancer. Among various PET parameters, SUVmax normalized to liver uptake after NCRT was the best predictor of the pCR.

Diagnostic value of 18F-FDG PET/CT in solitary pulmonary lesions and analysis on the causes of misdiagnosis

Objective To evaluate the diagnostic value of 18F-FDG PET/CT in solitary pulmonary lesions and to analyze the causes of misdiagnosis.Methods Thirty-two patients with solitary pulmonary lesions detected by 18F-FDG PET/CT were enrolled into this study and reviewed retrospectively.All the lesions were confirmed by histopathology.The possible causes for wrong-interpretation based on 18F-FDG PET/CT findings were investigated.Statistical analysis was performed using SPSS 16.0.The correlations between the SUVmax of early phase ( SUVmax,early) or the percentage change in SUVmax between early and delayed phases( ASUVmax ) and the lesion size were tested by Pearson analysis,respectively.Results 18F-FDG PET/CT had a detection accuracy of 68.75％ (22/32) for solitary pulmonary lesions.Among 32 cases,there were 5 false negatives and 5 false positives based on 18F-FDG PET/CT.The SUVmax,early was less than 2.5 in 6 of 22 malignant pulmonary lesions.The SUVmax,early in 2 of 10 benign pulmonary lesions was ≥2.5.The △SUVmax was less than 15％ in 5 of 22 malignant pulmonary lesions.As for the 10 benign pulmonary lesions,△SUVmax was ≥15％ in 4 cases.The average size (largest dimension) of 32 pulmonary lesions was ( 1.98 ± 1.08) cm,with 26 lesions smaller than or equal to 3 cm and 6 lesions larger than 3 cm.The SUVmax was positively correlated with the lesion size ( r =0.690,P ＜ 0.01 ),but there was no correlation between △SUVmax and the lesion size (r =- 0.081,P ＞ 0.05).Conclusions 18F-FDG PET/CT plays an important role in the diagnosis of solitary pulmonary lesion.However,SUVmax alone has its limitations; it is best to combine measurements with CT and other diagnostic parameters. Key words: Lung neoplasms; Lung diseases ; Tomography,emission-computed ; Tomography,X-ray computed; Deoxyglucose

Potential Role of FDG PET Imaging in Predicting Metastatic Potential and Assessment of Therapeutic Response to Neoadjuvant Chemotherapy in Ewing Sarcoma Family of Tumors

The aim of this study was to retrospectively correlate FDG uptake in primary Ewing sarcoma family of tumors (ESFT) with tumor behavior, and to evaluate whether FDG PET can be used to predict response to neoadjuvant chemotherapy (NACT) in this patient group. Out of the total 54 patients of recently diagnosed ESFT who underwent pretreatment FDG PET imaging, group I included patients without metastasis at presentation (n = 34) and group II included those with metastasis at presentation (n = 20). Fourteen of these patients had undergone FDG PET after 4 cycles of induction chemotherapy and surgical resection of primary tumor. In this subgroup of 14 patients, maximum standardized uptake value (SUVmax) of primary tumor was estimated before and after 4 cycles of induction chemotherapy and was correlated with the histopathological response in terms of necrosis in the tumor specimen. Mean SUVmax in the primary tumor in group I patients was 6.84 and in group II patients, it was 11.31. The difference between mean SUVmax of these 2 groups was significant by Wilcoxon test analysis, with P < 0.01. In group II patients, SUVmax in metastasis with maximum FDG uptake was consistently lower as compared with that of primary tumor. In subgroup of 14 patients, Pearson correlation analysis showed that percentage change in SUVmax of primary tumor correlated well with percentage necrosis on histopathological examination (P < 0.01). FDG uptake in primary ESFT reflected its metastatic potential and hence the aggressive behavior. The significant correlation between change in metabolic activity of the primary tumor and histopathological response after neoadjuvant chemotherapy suggests that FDG PET may be an ideal noninvasive method to assess tumor behavior and response to therapy in ESFT.

Use of 18F-FDG PET to Predict Response to First-Line Tuberculostatics in HIV-Associated Tuberculosis

This prospective pilot study examined the relationship between the severity and extent of tuberculosis as assessed by (18)F-FDG PET at the time of diagnosis and response to treatment or treatment failure at 4 mo. Twenty-four consecutive HIV patients with newly diagnosed tuberculosis were prospectively included in the study after providing written informed consent. Seventeen patients had pulmonary tuberculosis, and 7 patients had extrapulmonary tuberculosis. All patients underwent whole-body (18)F-FDG PET; none were receiving tuberculostatics at the time of the PET investigation. After undergoing (18)F-FDG PET, the patients were given tuberculosis treatment (the classic triad: isoniazid, rifampicin, and ethambutol) and reevaluated for treatment response: monthly assessment of sputum, smears, and cultures in patients who proved positive at the time of diagnosis, and clinical and radiologic (when relevant) assessment 4 mo after treatment instigation in all patients. Quantitative (18)F-FDG PET results (averaged (18)F-FDG maximum standardized uptake value [SUVmax] derived from early and delayed imaging), percentage change in SUVmax, and number of involved lymph node bastions were related to treatment response or failure. Age, sex, viral load, CD4 status, duration of HIV treatment, SUVmax of lung and splenic lesions (early and delayed), and percentage change in SUVmax of lymph nodes were not significantly different between responders and nonresponders (P ≥ 0.3). In contrast, SUVmax of involved lymph node bastions (both early and delayed) and number of involved lymph node bastions were significantly higher in nonresponders than in responders (respective P values were 0.03, 0.04, and 0.002). Using a cutoff of 5 or more involved lymph node bastions, responders could be separated from nonresponders with a sensitivity, specificity, and positive and negative predictive value of, respectively, 88%, 81%, 70%, and 93%. Using a cutoff of 8.15 for early SUVmax of lymph node bastions and of 10 for late SUVmax of lymph node bastions, a comparable sensitivity of 88% came at the cost of a lower specificity: 73% and 67%, respectively. In this pilot study, a cutoff of 5 or more involved lymph node bastions allowed for separation of tuberculostatic responsive and nonresponsive tuberculosis-infected HIV patients with a sensitivity of 88%, a specificity of 81%, and a negative predictive value of 93%. These findings warrant confirmation by additional studies on larger cohorts of patients.

Dual time point FDG-PET/CT imaging… Potential tool for diagnosis of breast cancer

This prospective study was designed to assess the utility of the dual time point imaging technique using 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) to detect primary breast cancer and to determine whether it is useful for the detection of small and non-invasive cancers, as well as cancers in dense breast tissue. One hundred and eleven patients with newly diagnosed breast cancer underwent two sequential PET/CT examinations (dual time point imaging) for preoperative staging. The maximum standardized uptake value (SUVmax) of FDG was measured from both time points. The percentage change in SUVmax (DeltaSUVmax%) between time points 1 (SUVmax1) and 2 (SUVmax2) was calculated. The patients were divided into groups: invasive (n=82), non invasive (n=29); large (>10mm; n=80), small (<or=10mm; n=31); tumours in dense breasts (n=61), and tumours in non-dense breasts (n=50). The tumour:background (T:B) ratios at both time points were measured and the DeltaSUVmax%, DeltaT:B% values were calculated. All PET study results were correlated with the histopathology results. Of the 111 cancer lesions, 88 (79.3%) showed an increase and 23 (20.7%) showed either no change [10 (9%)] or a decrease [13 (11.7%)] in the SUVmax over time. Of the 111 contralateral normal breasts, nine (8.1%) showed an increase and 102 (91.9%) showed either no change [17 (15.3%)] or a decrease [85 (76.6%)] in the SUVmax over time. The mean+/-SD of SUVmax1, SUVmax2, Delta%SUVmax were 4.9+/-3.6, 6.0+/-4.5, and 22.6+/-13.1% for invasive cancers, 4.1+/-3.8, 4.4+/-4.8, and -2.4+/-18.5% for non-invasive cancers, 2.3+/-1.9, 2.7+/-2.3, and 12.9+/-21.1% for small cancers, 5.6+/-3.7, 6.8+/-4.8, and 17.3+/-17.1% for large cancers, 4.9+/-3.7, 5.8+/-4.8, and 15.1+/-17.6% for cancers in dense breast, and 4.5+/-3.6, 5.4+/-4.5, and 17.2+/-19.2% for cancers in non-dense breast. The receiver-operating characteristic (ROC) analysis suggested DeltaSUVmax% of 8% as the only significant cut-off for discrimination between invasive and non-invasive cancer (sensitivity 84.1%, specificity 75.9%, p<0.0001). Dual time point FDG-PET/CT improves the discrimination between non-invasive and invasive cancers, and provided superior sensitivity for the detection of small cancers and cancers in dense breast.

Comparison of triple‐negative and estrogen receptor‐positive/progesterone receptor‐positive/HER2‐negative breast carcinoma using quantitative fluorine‐18 fluorodeoxyglucose/positron emission tomography imaging parameters

AbstractBACKGROUND.This study was designed to investigate the fluorine‐18 fluorodeoxyglucose (FDG)‐positron emission tomography (PET) imaging characteristics of triple‐negative (estrogen receptor‐negative [ER−]/progesterone receptor‐negative [PR−]/HER2‐negative [HER2−]) breast carcinoma and compare the results with characteristics of ER+/PR+/HER2− breast carcinomas, which usually carry a favorable prognosis.METHODS.Patients with newly diagnosed breast carcinoma who had undergone dual‐time‐point FDG‐PET before any therapeutic intervention and were identified as either ER−/PR−/HER2− or ER+/PR+/HER2− (the control group) on histopathology of the surgical specimen, were considered candidates for inclusion in this analysis. These patients underwent FDG‐PET as a component of a prospective study that evaluated the role of multimodality imaging for characterizing primary breast lesions and locoregional staging. Breast cancer lesions were imaged twice at approximately 63 minutes and 101 minutes after the administration of FDG. Maximum standardized uptake values (SUVmax) were measured at both time points (SUVmax1 and SUVmax2) to analyze the data generated. After FDG‐PET imaging, the patients underwent either breast‐conserving surgery or mastectomy, and histopathology reports were used to provide the definitive diagnosis against which the PET study results were compared.RESULTS.In total, 88 patients with breast cancer (29 patients with ‘triple‐negative’ breast cancer and 59 patients with ER+/PR+/HER2− breast malignancies) were selected among 206 individuals who were enrolled in the study protocol. The ‘triple‐negative’ group comprised 14.08% of the total study population. The age of the patients with this subtype of tumor ranged from 33 years to 75 years (mean age±standard deviation, 51.6 ± 10.1 years), and tumors in this subgroup ranged in size from 0.9 cm to 6 cm (mean size, 1.99 cm). Among the histopathologic subtypes, 25 tumors were infiltrating ductal carcinoma (86%), and 1 tumor each (3.5% each subtype) was lobular, mixed ductal‐lobular, medullary, and tubular. For the calculation of FDG‐PET parameters in this group, only patients who had undergone FDG‐PET studies before any intervention were considered, and 18 patients in the triple‐negative group met this criterion. According to same criterion, a control group of 59 patients with ER+/PR+/HER2− cancer who had focal FDG uptake were selected for comparison with the triple‐negative population. The breast cancer lesions were observed as areas with focally enhanced uptake of FDG in all patients (sensitivity, 100%) in the triple‐negative group. The mean (±standard deviation) SUVmax1 of the primary lesion for the triple‐negative group was 7.27 ± 5.6, the mean SUVmax2 was 8.29 ± 6.4, and the percentage change in SUVmax (%ΔSUVmax) was 14.3 ± 15.8%. In the control group of 59 patients with ER+/PR+/HER2− breast carcinoma, the mean values for SUVmax1, SUVmax2, and %ΔSUVmax were 2.68 ± 1.9, 2.84 ± 2.2, and 3.7 ± 13.0%, respectively. The mean values for SUVmax1, SUVmax2, and %Dgr;SUVmax in the triple‐negative group were significantly higher compared with the values in the nontriple‐negative control group (P = .0032, P = .002, and P = .017, respectively). When the 2 subgroups were compared according to tumor size, grade, and stage, the SUVmax1 was significantly higher in the triple‐negative group for both size categories (5.4 vs 1.9, P = .006; and 9.2 vs 3.5, P = .04) and for grade 3 tumors (9.1 vs 3.9, P = .022). The %ΔSUVmax values for patients in the triple‐negative group who had tumors that measured ≤2 cm and &gt; 2 cm were 14.8 and 13.8, respectively; and the corresponding values for patients in the control group were 0.6 and 6.7, respectively. Although the mean %ΔSUVmax clearly was higher in the triple‐negative group for both tumor size categories, comparison between the 2 groups demonstrated a statistically significant difference in tumors that measured ≤2 cm (P = .016). The authors also observed that, in the triple‐negative group, tumor grades were correlated significantly with the magnitude of SUVmax1 and SUVmax2 (P = .012 and P = .01, respectively). Stage for stage, tumors from the triple‐negative group appeared to have a higher mean SUVmax1 compared with tumors from nontriple‐negative control group. However, the trend reached statistical significance in patients with stage II disease.CONCLUSIONS.Triple‐negative breast tumors were associated with enhanced FDG uptake commensurate with their aggressive biology and were detected with very high sensitivity by using FDG‐PET imaging. Cancer 2008. © 2007 American Cancer Society.

Assessment of response using FDG-PET and CT in a phase I study of AMN107 alone or in combination with imatinib (IM) in patients with imatinib-resistant (IM-R) gastrointestinal stromal tumors (GIST)

3087 Background: Although IM induces durable clinical benefit in pts with metastatic GIST, resistance to this single agent may emerge over time and new approaches are needed. AMN107 is a new agent rationally designed to inhibit in a structurally different manner the tyrosine kinase activities of KIT, PDGFR, and Bcr-Abl. Since AMN107 has demonstrated the ability to inhibit the proliferation of both IM-sensitive and IM-R GIST cells in vitro, a clinical trial was begun to test this agent with rapid assessment of impact using FDG-PET. Methods: Pts with IM-R GIST were treated with AMN107 alone (400 mg p.o. bid), or a combination of IM (400 mg p.o. bid) and inter-cohort dose escalations of AMN107 (200 mg qd, 400 mg qd, and 400 mg p.o. bid). FDG-PET and CT were performed at baseline and after 1 and 4 wks on therapy. Maximum standardized uptake values (SUVmax) were measured in 11 pts in up to 5 lesions with the greatest FDG uptake/pt (n=46 lesions). For each patient, the summation SUVmax (sSUVmax) of all lesions was calculated at each time point. Percentage change in SUVmax and sSUVmax was calculated at wks 1 and 4 compared to baseline. Metabolic response was assessed using EORTC thresholds for % SUVmax change (PR≤ -25% &lt;SD&lt; +25%≤ PD). The longest diameters of all lesions analyzed by PET were measured on corresponding CT images, summed at each time point, and the % change was calculated at wks 1 and 4 compared to baseline. CT response was assessed using conventional RECIST thresholds. Results: At 1 wk, PET imaging of 11 evaluable pts documented metabolic PR in 3/11, SD in 7/11, and PD in 1/11. After 4 wks on therapy, 2 pts whose PET was stable after 1 wk had converted to metabolic PR, and all other imaging results were unchanged. The CT response for all 11 pts was SD after 1 and 4 wks on therapy. Conclusions: These findings suggest that a metabolic response to AMN107, or the combination of AMN107 plus IM, is seen with FDG-PET while CT anatomic response remains SD at 1 and 4 wks. [Table: see text] [Table: see text]