SUV Peak Research Articles

Impact of the Definition of Peak Standardized Uptake Value on Quantification of Treatment Response

PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUV(max)), which is adversely affected by noise. Peak SUV (SUV(peak)) has been recommended as a more robust alternative, but its associated region of interest (ROI(peak)) is not uniquely defined. We investigated the impact of different ROI(peak) definitions on quantification of SUV(peak) and tumor response. Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. (18)F-FLT-avid lesions (∼2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUV(peak). For each tumor, 24 different SUV(peaks) were determined by changing ROI(peak) shape (circles vs. spheres), size (7.5-20 mm), and location (centered on SUV(max) vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUV(peaks) and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROI(peak) definition, a population average SUV(peak) and tumor response were determined over all tumors. A substantial variation in both SUV(peak) and tumor response resulted from changing the ROI(peak) definition. The variable ROI(peak) definition led to an intratumor SUV(peak) variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUV(peak) response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROI(peak) definition led to a population average SUV(peak) variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUV(peak) response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROI(peak) caused more variation in intratumor response than did the location or shape of ROI(peak). Population average tumor response was independent of size, shape, and location of ROI(peak). Quantification of individual tumor response using SUV(peak) is highly sensitive to the ROI(peak) definition, which can significantly affect the use of SUV(peak) for assessment of treatment response. Clinical trials are necessary to compare the efficacy of SUV(peak) and SUV(max) for quantification of response to therapy.

PD09-05: SU2C Phase Ib Study of pan-PI3K Inhibitor BKM120 Plus Aromatase Inhibitor Letrozole in ER+/HER2− Metastatic Breast Cancer (MBC).

Abstract Background: Experimental evidence and clinical data suggest that PIK3CA mutations (present in approximately 35% of ER+ cancers) are associated with de novo or acquired resistance to antiestrogen therapy. Considering that most breast cancers resistant to antiestrogen therapy retain ER and estrogen sensitivity, treatment of ER+ breast cancers with single-agent PI3K-targeted therapy may be insufficient to inhibit tumor growth. Materials and Methods: To evaluate safety/tolerability, we initiated a phase Ib clinical trial of letrozole with the pan-PI3K inhibitor BKM120 (Novartis) in post-menopausal patients with ER+/HER2−MBC. Letrozole (2.5 mg/d) and BKM120 (100 mg/d) were given on a 28-day cycle. When necessary, BKM120 was reduced to 80 and 60 mg/day. Treatment was continued until unacceptable toxicity or progression of disease. Disease was assessed every 2 months. FDG-PET imaging was performed at 2 weeks to identify changes indicative of pharmacodynamic modulation of PI3K/AKT. Results: Twenty patients have been accrued; all but 2 patients had previously progressed on an aromatase inhibitor (AI) in the metastatic setting. Median age was 56 years; 85% of patients had metastatic bone disease, 70%, visceral metastases. Twelve patients are still on treatment, 2 of these are currently on BKM120 80 mg/day. Three patients discontinued treatment within 2 months of initiation due to grade 3 transaminitis, grade 2 irritability, and grade 2 hyperglycemia, despite dose reductions and/or optimal treatment. Most common toxicities are summarized in the table below. Transaminase elevation was the only DLT at 100 mg/d BKM120. Of the 12 evaluable patients that completed at least 8 weeks of treatment, 1 had a partial response, 7 had stable disease, and 4 had disease progression (RECIST). So far 3 patients have been on treatment for >4 months. Over 50% of patients had >25% reduction in their peak SUV at the 2-week FDG-PET scan. Discussion: The letrozole + BKM120 combination is active in patients with ER+/HER2− MBC refractory to previous therapy with an AI. At this time, all patients’ primary diagnostic tumor biopsies and/or metastatic biopsies are being analyzed for the presence of PIK3CA, AKT1, or PTEN mutations and PTEN loss (immunohistochemistry). FDG-PET imaging at 2 weeks appears to be a useful pharmacodynamic biomarker of PI3K pathway inhibition. Correlation of mutational analysis with clinical benefit will be presented at the meeting. Despite an overall safe side effect profile, an alternative administration schedule of BKM120 with letrozole is planned to enhance tolerability of the combination. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD09-05.

SU‐E‐J‐97: Predictive and Prognostic Clinical Values of 18F‐FDG PET Based Measurements in Locally Advanced Esophageal Cancer Are Not Improved by Partial Volume Effects Correction

Purpose: We have previously demonstrated that functional tumor volume (TV) and Total Lesion Glycolysis (TLG=TV×SUVmean) measured on pretreatment 18F‐FDG PET scans were significant predictors of response and prognostic factors of survival, whereas SUV measurements were not. The objective of this study was to investigate the impact of partial volume effects (PVE) correction (PVC) on this clinical value. Methods: 50 patients with esophageal cancer treated with concomitant radiochemotherapy were retrospectively analyzed. 18F‐FDG PET baseline scans were corrected for PVE with iterative deconvolution with wavelet‐based denoising. Tumors were subsequently delineated using the Fuzzy Locally Adaptive Bayesian (FLAB) algorithm on both original and corrected images. Maximum and peak SUV, TV, mean SUV, and TLG were extracted and compared. The value of each parameter (with or without PVC) was investigated using Kruskal‐Wallis tests regarding response and Kaplan‐Meier curves regarding survival. Results: Whereas PVC had a significant quantitative impact on the absolute values of each parameter (up to more than 100% for SUVmax), the respective clinical value was not significantly modified whether for overall survival or response to therapy. No significant improvement was observed after PVC for the already established significant predictive and prognostic value of TV and TLG. Similarly, the non significant predictive and prognostic value of the various SUV measurements was not improved by PVC and was even lowered in some cases. Conclusions: PVC did not modify significantly the previously established clinical value of tumor volume or TLG. In addition, the limited value of SUV measurements in this context may therefore not be explained by the lack of PVC since PVC did not improve their clinical value and in most cases it even lowered it.

SU‐E‐I‐167: Impact of Peak SUV Definition on Quantification of Treatment Response

Purpose: PET‐based treatment response assessment typically measures the change in SUVmax, which is adversely affected by noise. SUVpeak has been recommended as a more robust alternative, but currently its associated region‐of‐interest (ROIpeak) is not uniquely defined. We investigated the impact of different ROIpeak definitions on quantification of SUVpeak and tumor response. Methods: Seventeen patients with solid malignancies were treated with an anti‐proliferative, molecular targeted agent. Using the cellular proliferation marker [F‐18]FLT, whole‐body PET/CT scans were acquired at baseline and during treatment. Lesions with highest FLT uptake (∼2/patient) were segmented on PET images and tumor response was assessed via the relative change in SUVpeak. For each tumor, 24 different SUVpeak and response values were determined by changing ROIpeak shape, size, and location. Within each tumor, variation of the 24 values was measured using range, coefficient of variation (CV) for SUVpeak, and standard deviation (SD) for response. For each ROIpeak definition, population average SUVpeak and response were determined over all tumors. Results: Substantial variation in both SUVpeak and response resulted from changing the ROIpeak definition. Intra‐tumor SUVpeak variation (CV: 17%) and response variation (SD: 9%) ranged as far as 50% from the mean. Population average SUVpeak variation (CV: 14%) ranged as far as 30% from the mean but population average tumor response variation (SD: 2%) ranged only 3% from the mean. Size of ROIpeak caused more variation in SUVpeak and response than location or shape of ROIpeak. Conclusion: Quantification of individual tumor response using SUVpeak is highly sensitive to ROIpeak definition, which can significantly impact the use of SUVpeak for treatment response assessment. However, population average response is robust to ROIpeak definition. Standardization of SUVpeak is crucial for consistent assessment of treatment response. Clinical trials are necessary to compare the efficacy of SUVpeak and SUVmax for quantification of response to therapy.

18F]fluoro-L-thymidine (FLT) uptake in baseline positron emission tomography (PET) as a prognostic marker in patients with advanced non-small cell lung cancer (NSCLC) treated first-line with erlotinib.

7591 Background: Since the introduction of targeted therapy into the treatment of advanced NSCLC molecular imaging tools gain in importance for assessment of pharmacodynamics, prognosis and prediction of therapeutic outcome. We evaluated the prognostic value of 3'-deoxy-3'-[18F]fluoro-L-thymidine (FLT) uptake measured by positron emission tomography (PET) as a noninvasive proliferation marker in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. Methods: We retrospectively analyzed FLT uptake in 41 chemonaive patients with advanced NSCLC (stage IV) treated with erlotinib first-line prior to systemic therapy. The peak SUV of the lesion with the highest SUV (SUVpeak) as well as sex, age, ECOG performance state at presentation, EGFR mutational status and adenocarcinoma/BAC histology were analyzed in univariate analysis using Kaplan-Meier statistics and log rank test for its association with survival. Multivariate analysis was performed using Cox regression. Results: Median follow-up was 21.9 months. In univariate analysis, patients with an SUVpeak ≤3.1 had a significantly better overall survival (15.67 months [95% CI 6.4 to 25 months]) compared to patients with an SUVpeak >3.1 (3.2 months [95% CI 0 to 8.2 months]) (p=0.008, log rank). In addition, age was significantly associated with overall survival (p=0.046 log rank test). In this cohort none of the clinical parameters gender, histology, ECOG performance status or EGFR mutational status were significantly associated with overall survival. In multivariate analysis including age and SUVpeak, SUVpeak was a significantly strong prognostic factor for overall survival (p=0.020). Conclusions: FLT uptake of the most active tumor manifestation site is a strong prognostic marker for overall survival among patients with advanced NSCLC treated with erlotinib first-line.

Usefulness of 18-F FDG PET/CT in the pre-treatment evaluation of thymic epithelial neoplasms

Background To assess the usefulness of 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) for differentiating the grade of malignancy of thymic epithelial neoplasm, and to determine whether 18F-FDG PET/CT can have a role in pretreatment evaluation and possibly modify treatment strategy. Materials and methods The data of 26 consecutive patients (14 males and 12 females) diagnosed with a thymic epithelial neoplasm were prospectively collected and analyzed retrospectively. All patients underwent standard clinical assessment and 18F-FDG PET/CT. The patients were divided into two subgroups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1) and high-risk thymoma (types B2, B3 and C). The maximum standardized uptake value (SUV max) of the tumor, the mean SUV of mediastinum, and the tumor/mediastinum (T/M) ratio (ratio of peak SUV of the tumor to mean SUV of mediastinum) were compared to determine whether the two subgroups (low-risk versus high-risk tumors) could be distinguished by 18F-FDG PET/CT, and to test for possible correlations between 18F-FDG uptake and disease stage. Results There was a strong statistical correlation between SUV max and patient subgroup and between SUV max and disease stage, and an even stronger correlation between SUV max and patient subgroup and the T/M ratio; a T/M ratio of 2.75 emerged as the cut-off value for differentiating between low-risk and high-risk thymomas. Conclusions 18F-FDG PET/CT can be used a “metabolic biopsy” to divide thymic epithelial neoplasm into two subgroups of high and low risk and is useful in pretreatment staging.

Repeatability of 18F-FDG PET in a Multicenter Phase I Study of Patients with Advanced Gastrointestinal Malignancies

(18)F-FDG PET is often used to monitor tumor response in multicenter oncology clinical trials. This study assessed the repeatability of several semiquantitative standardized uptake values (mean SUV [SUV(mean)], maximum SUV [SUV(max)], peak SUV [SUV(peak)], and the 3-dimensional isocontour at 70% of the maximum pixel value [SUV(70%)]) as measured by repeated baseline (18)F-FDG PET studies in a multicenter phase I oncology trial. Double-baseline (18)F-FDG PET studies were acquired for 62 sequentially enrolled patients. Tumor metabolic activity was assessed by SUV(mean), SUV(max), SUV(peak), and SUV(70%). The effect on SUV repeatability of compliance with recommended image-acquisition guidelines and quality assurance (QA) standards was assessed. Summary statistics for absolute differences relative to the average of baseline values and repeatability analysis were performed for all patients and for a subgroup that passed QA, in both a multi- and a single-observer setting. Intrasubject precision of baseline measurements was assessed by repeatability coefficients, intrasubject coefficients of variation (CV), and confidence intervals on mean baseline differences for all SUV parameters. The mean differences between the 2 SUV baseline measurements were small, varying from -2.1% to 1.9%, and the 95% confidence intervals for these mean differences had a maximum half-width of about 5.6% across the SUV parameters assessed. For SUV(max), the intrasubject CV varied from 10.7% to 12.8% for the QA multi- and single-observer datasets and was 16% for the full dataset. The 95% repeatability coefficients ranged from -28.4% to 39.6% for the QA datasets and up to -34.3% to 52.3% for the full dataset. Repeatability results of double-baseline (18)F-FDG PET scans were similar for all SUV parameters assessed, for both the full and the QA datasets, in both the multi- and the single-observer settings. Centralized quality assurance and analysis of data improved intrasubject CV from 15.9% to 10.7% for averaged SUV(max). Thresholds for metabolic response in the multicenter multiobserver non-QA settings were -34% and 52% and in the range of -26% to 39% with centralized QA. These results support the use of (18)F-FDG PET for tumor assessment in multicenter oncology clinical trials.

The CT Findings and the Peak SUV on PET/CT according to the Levels of Cyfra 21-1 and CEA in Patients with Non-Small Cell Lung Carcinoma

Purpose: We wanted to evaluate the CT findings and the peak SUV according to the levels of cyfra 21-1 and CEA in patients with non-small cell lung carcinoma (NSCLC). Materials and Methods: We evaluated the TNM staging, cell types, the CT findings and peak SUV of the NSCLC in 234 patients with NSCLC according to the tumor marker levels. The correlations of the CT findings and the peak SUV with the tumor markers were evaluated in 35 patients with stage I disease. Results: The sensitivities of the combined tumor markers cyfra 21-1 and CEA in the NSCLC for each TNM staging (I-IV) were 48.5%, 66.7%, 78.3% and 84.3%, respectively (p

Treatment Monitoring by 18F-FDG PET/CT in Patients with Sarcomas: Interobserver Variability of Quantitative Parameters in Treatment-Induced Changes in Histopathologically Responding and Nonresponding Tumors

Measurements of tumor glucose use by (18)F-FDG PET need to be standardized within and across institutions. Various parameters are used for measuring changes in tumor glucose metabolic activity with (18)F-FDG PET in response to cancer treatments. However, it is unknown which of these provide the lowest variability between observers. Knowledge of the interobserver variability of quantitative parameters is important in sarcomas as these tumors are frequently large and demonstrate heterogeneous (18)F-FDG uptake. A total of 33 patients (16 men, 17 women; mean age, 47 +/- 18 y) with high-grade sarcomas underwent (18)F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Two independent investigators measured the following parameters on the pretreatment and posttreatment scans: maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), SUVmean in an automatically defined volume (SUVauto), and tumor-to-background ratio (TBR). The variability of the different parameters was compared by concordance correlation coefficient (CCC), variability effect coefficient, and Bland-Altman plots. Baseline SUVmax, SUVpeak, SUVmean, SUVauto, and TBR averaged 10.36, 7.78, 4.13, and 6.22 g/mL and 14.67, respectively. They decreased to 5.36, 3.80, 1.79, and 3.25 g/mL and 6.62, respectively, after treatment. SUVmax, SUVpeak, and SUVauto measurements and their changes were reproducible (CCC > or = 0.98). However, SUVauto poorly differentiated between responding and nonresponding tumors. The high intratumoral heterogeneity of (18)F-FDG resulted in frequent failure of the thresholding algorithm, which necessitated manual corrections that in turn resulted in a higher interobserver variability of SUVmean (CCCs for follow-up and change were 0.96 and 0.91, respectively; P < 0.005). TBRs also showed a significantly higher variability than did SUVpeak (CCCs for follow-up and change were 0.94 and 0.86, respectively; P < 0.005). SUVmax and SUVpeak provided the most robust measurements of tumor glucose metabolism in sarcomas. Delineation of the whole-tumor volume by semiautomatic thresholding did not decrease the variability of SUV measurements. TBRs were significantly more observer-dependent than were absolute SUVs. These findings should be considered for standardization of clinical (18)F-FDG PET/CT trials.

Characterization of radiologically indeterminate lung lesions: 99mTc-depreotide SPECT versus 18F-FDG PET

To evaluate the diagnostic accuracy of 99m Tc-depreotide vs PET-18FDG scans in patients with suspicion of lung cancer. Prospective study in 29 patients (age: 38-80 years) diagnosed of inderteminate lung lesions. Diagnosis was established by histology based on samples of surgical resection, fine needle aspiration (FNA) or broncoalveolar lavage (BAL). Within a maximum of 10 days, without pre-established fixed order the following exams were performed: 1) Whole body and chest SPECT-CT with Tc-depreótide (DEP-SPECT) and 2) PET-CT study with F-FDG (PET-FDG). Every exam was evaluated by Nuclear Medicine especialist blinded to patient data. Malignancy was confirmed in 20 patients. PET-FDG was positive in all cases. DEP-SPECT was positive in 17 and falselly negative in 3, one carcinoid tumor, one undifferentiated non-small cell adenocarcinoma, and a moderately differentiated adenocarcinoma. In the remaining 9 patients benignancy was confirmed; both studies were normal in 8 and falselly positive in one case of non-specific inflammatory lung process. In 9 out of the 20 cases with malignancy extrapulmonar uptake was seen, with a total number of 19 lesions. In two cases the extrapulmonar uptake were non ganglionar metastasis (bone and adrenal) and in 7 due to mediastinic ganglionar involvement. ROC analysis using peak SUV FDG (cut-off point of 3.5) uptake and target/background depreotide uptake (cut-off point of 1.3) provided, sensitivity and specificity values of 95% and 89% of 84% and 88% for PET and SPECT respectively. It does not exist statistically significant differences between both methods (Z-test SPSS). In summary, FDG-PET has a greater sensitivity and diagnostic accuracy for assessing malignancy of indeterminate lung lesions, and for detection of extrapulmonary involvement, DEP-SPECT represents a good diagnostic alternative for centers where PET is not available.

The number of abnormalities on pre-treatment PET scan predicts for overall survival of patient with localized esophageal and GE junction carcinoma (E/GEJC)

4019 Background: The value of pre-treatment PET (pre-PET) in predicting outcome of patients (pts) with E/GEJC has not been established. We hypothesized that the extent of pre-PET abnormality would predict for the overall survival (OS) and disease-free survival (DFS). Methods: 50 pts with localized E/GEJC (cIIa, cIIb, cIII), who had a pre-PET then preoperative chemoradiotherapy (CTRT), were analyzed for its association with DFS, OS, and pathCR. PET analyses accounted for the SUV of the primary Site (PSUV), peak SUV (PkSUV), number of hotspots (NSUV), the total of regional SUV other than the primary site (RSUV), and the total SUV (TSUV). Fisher's exact test and Log-rank test were used. Each of above pre-PET parameters was then correlated with DFS, OS, and pathCR. We also correlated pretreatment EUS stage with pre-PET parameters. Results: The NSUV and RSUV were significantly associated with OS of pts (p=0.028, p=0.006 respectively). Pts with ≥2 hotspots had a poor outcome with hazard function of 4.77. Pts with a RSUV of >1 also had a higher hazard function (2.12) than those with RSUV of ≤1. OS did not correlate with PSUV, PkSUV, or TSUV. No correlation was observed with any of the pre-PET parameters and pathCR (all p-values >0.05). Likewise, none of the pre-PET parameters predicted for DFS. In addition, there was no significant correlation between pretreatment EUS stage and pre-PET parameters (p>0.05 in all cases). Conclusion: Our data demonstrate that the RSUV and NSUV are significantly associated with OS of pts with E/GEJC. Therefore, pre-PET findings should now be used as a stratification factor in pts with E/GEJC participating in phase III randomized trials. No significant financial relationships to disclose.

The number of abnormalities on pre-treatment PET scan predicts for overall survival of patient with localized esophageal and GE junction carcinoma (E/GEJC)

4019 Background: The value of pre-treatment PET (pre-PET) in predicting outcome of patients (pts) with E/GEJC has not been established. We hypothesized that the extent of pre-PET abnormality would predict for the overall survival (OS) and disease-free survival (DFS). Methods: 50 pts with localized E/GEJC (cIIa, cIIb, cIII), who had a pre-PET then preoperative chemoradiotherapy (CTRT), were analyzed for its association with DFS, OS, and pathCR. PET analyses accounted for the SUV of the primary Site (PSUV), peak SUV (PkSUV), number of hotspots (NSUV), the total of regional SUV other than the primary site (RSUV), and the total SUV (TSUV). Fisher's exact test and Log-rank test were used. Each of above pre-PET parameters was then correlated with DFS, OS, and pathCR. We also correlated pretreatment EUS stage with pre-PET parameters. Results: The NSUV and RSUV were significantly associated with OS of pts (p=0.028, p=0.006 respectively). Pts with ≥2 hotspots had a poor outcome with hazard function of 4.77. Pts with a RSUV of >1 also had a higher hazard function (2.12) than those with RSUV of ≤1. OS did not correlate with PSUV, PkSUV, or TSUV. No correlation was observed with any of the pre-PET parameters and pathCR (all p-values >0.05). Likewise, none of the pre-PET parameters predicted for DFS. In addition, there was no significant correlation between pretreatment EUS stage and pre-PET parameters (p>0.05 in all cases). Conclusion: Our data demonstrate that the RSUV and NSUV are significantly associated with OS of pts with E/GEJC. Therefore, pre-PET findings should now be used as a stratification factor in pts with E/GEJC participating in phase III randomized trials. No significant financial relationships to disclose.

Evaluation of Response to Neoadjuvant Therapy by Quantitative 2-Deoxy-2-[ 18F]Fluoro-D-Glucose with Positron Emission Tomography in Patients with Esophageal Cancer

Purpose: This work evaluates positron emission tomography (PET) with 2-deoxy-2-[ 18F]fluoro-D-glucose (FDG) in assessing response to therapy in patients with esophageal cancer. Procedures: Twenty-four patients underwent FDG-PET before (pre-Rx) and after (post-Rx) chemoradiation therapy; 20 then underwent esophagectomy. The response of the primary tumors was visually assessed, and tumor volume, peak tumor standardized uptake value (SUV peak), average SUV (SUV ave), and total lesion glycolysis were determined pre-treatment and post-treatment. Patients were divided into groups according to the absence (Group A) or presence (Group B) of residual tumor after neoadjuvant therapy. Results: Among the quantitative PET parameters for Group A (n = 6) and Group B (n = 18), only change in tumor volume identified complete responders. Quantitative PET indices were not different in patients with or without post-Rx esophagitis. Conclusions: The change in tumor volume identifies patients with complete response to neoadjuvant therapy, and quantitative evaluation of the primary tumor cannot separate post-Rx inflammation from residual tumor.

ENCEPHALITIS LETHARGICA

<b>1270</b> <h3><b>Purpose:</b></h3> Immunologic response to anti-PD-1 therapy can occur rapidly with previous reports showing T cell responses detectable in as little as several weeks. Given that activated lymphocytes are known to be FDG avid, we hypothesized that FDG PET/CT could be used to visualize an early “flare” response to immunotherapy, in which FDG activity within tumors increases due to infiltration by activated lymphocytes, and that this flare response would predict treatment response. Thus, a prospective clinical trial was initiated for patients with advanced melanoma using 18F-FDG PET/CT scans and blood biomarkers obtained before and ~1 week after a single dose of anti-PD-1 therapy. <b>Materials and Methods:</b> This IRB-approved study prospectively investigated 16 patients (10 males and 6 females, mean age 66 ± 16y) with metastatic melanoma after receiving 1 dose of anti-PD-1 therapy (pembrolizumab). FDG PET/CT imaging was performed at baseline (mean 12 ± 10 days before treatment), and after treatment (mean 8 ± 4 days after treatment) in all patients. Pembrolizumab was continued per standard clinical care. FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). A “flare” was defined as &gt;100% increase in tumor SUVmax between baseline and post-therapy scans. Blood samples were collected prior to treatment, and at multiple time points (7 days and 3, 6, 9, and 12 weeks) post-treatment, for analysis of immune biomarkers. Response was determined using RECIST 1.1 criteria, with a median follow-up of 19 months. <h3><b>Results:</b></h3> 7 patients had a complete response (CR) to anti-PD-1 therapy, 3 patients had a partial response (PR), and 6 patients had progressive disease (PD). 13% of patients (2/16) demonstrated a flare on FDG PET/CT (acquired 6-7 days post-therapy), with dramatic increases in tumor SUVmax (range: 130% - 281%), without change in tumor size. Both patients with flare responses achieved CR, with no evidence of disease after at least 10 months of follow-up. The remaining 5 patients with CR that did not have a flare were imaged at 7-8 days post-therapy, and all 5 patients demonstrated a drop in SUVmax (mean: -17.3 ± 37.7%) or a decrease in size (mean: -4.7 ± 3.8%), or both, suggesting that they may have been imaged after their immune response had already peaked. Even though patients were imaged at early post-therapy time points, small but measurable decreases in lesion size were seen in responding patients (mean change in size: -2.7 ± 4.0%), and increases in lesion size were seen in nonresponding patients (mean change in size: 13.8 ± 2.9%). Changes in SUVmax for patients that did not have a flare (range: -68% to 59%) were not predictive of response. Preliminary analysis of MTV and TLG did not provide additional benefit compared to SUVmax. Our FDG PET/CT flare observations correlated with flow cytometric evaluation of blood samples taken pre- and post-treatment, which identified a robust increase in responding Ki67+ CD8 T cells, with a peak at day 7 which was greater in magnitude compared to all of the other time points, including week 3. <h3><b>Conclusions:</b></h3> In patients with advanced melanoma, the immune response to anti-PD-1 therapy appears to occur early, with evidence of T cell reinvigoration in the blood at 1 week post-therapy; an associated flare response on FDG PET/CT imaging at 1 week post-therapy is predictive of a complete response to immunotherapy.