PERCIST Criteria Research Articles

FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer.

9618 Background: In a murine non-small cell lung cancer (NSCLC) model, we demonstrated synergy between localized radiotherapy and the dendritic cell growth factor fms-like tyrosine kinase 3 (FLT3) ligand. We now present results from a phase II study testing this combination in patients with advanced and treatment-refractory NSCLC. Methods: Advanced NSCLC patients with multifocal active disease after at least one line of systemic therapy and ECOG performance status 0-2 received 5 daily subcutaneous injections of CDX-301 (75 µg/kg) concurrent with stereotactic body radiotherapy (SBRT, 30-54 Gy in 1-5 fractions based on target size and location) directed at a single site of disease. Additional “cycles” of SBRT and CDX-301 could be administered at least four months after the initial study treatment, at the discretion of the treating physicians. The primary endpoint was progression-free survival four months after treatment initiation (PFS4), with a hypothesis that the PFS4 rate would exceed 40%. Secondary endpoints included overall survival (OS) duration, responses on PET (PERCIST criteria) and CT (RECIST criteria), and dose-limiting toxicities (grade ≥3 adverse events within 30 days). Lesions targeted with SBRT were excluded from response assessments. The intended sample size was 29 subjects. Blood samples were obtained for flow cytometry and other analyses of immune activation. Results: Twenty-nine subjects received study therapy between October 2016 and January 2020. Subjects received a median of 3 lines (range: 1-5) of systemic therapy prior to study enrollment, including immune checkpoint inhibitors targeting the PD-1/PD-L1 axis in 26 subjects (90%). At the time of this analysis, the actuarial PFS4 rate is 60%, which exceeds our pre-specified efficacy objective. With a median follow-up duration for living patients of 12 months, the actuarial 12-month OS rate is 55%. Partial response of lesions not targeted with SBRT (“abscopal effect”) was observed in 9 subjects (31%) using PET criteria and in 4 subjects (14%) using CT criteria. Seven subjects (24%) received a second course of SBRT and CDX-301 after initial study therapy. No dose-limiting toxicities have been observed. Only six subjects (21%) have received additional chemotherapy or immunotherapy after study treatment. Conclusions: The combination of CDX-301 and SBRT is well-tolerated and has activity as systemic therapy for advanced NSCLC. Additional studies to maximize the efficacy of this in situ vaccination approach with the addition of an agonist anti-CD40 antibody (CDX-1140) are planned. Clinical trial information: NCT02839265 .

Textural features in FDG-PET/CT can predict outcome in melanoma patients to treatment with Vemurafenib and Ipililumab.

Recently, textural parameters assessed in FDG-PET/CT as surrogate marker for tumor heterogeneity have been shown to provide prognostic power. Therefore, we investigated the use of such parameters in FDG-PET/CT examinations before the start of immunotherapy with vemurafenib or ipilimumab in patients with malignant melanoma. In this retrospective analysis 26 patients with histologically proven advanced melanoma were included. FGD-PET/CT was performed before the start of treatment either with vemurafenib (n = 9) or ipilimumab (n = 17) and tumors were analyzed for textural parameters as well as conventional PET features. Lesions were classified as responding or not responding following PERCIST criteria. ROC analysis was performed to analyze the predictive power and cut-off values. In addition, the change of maximum SUV of the lesions between pretherapeutic PET/CT and another PET/CT performed about 12 weeks after start of treatment was evaluated and correlated with the pretreatment parameters. In both groups, six textural parameters showed statistically significant predictive power as well as the metabolic tumor volume. In the group treated with vemurafenib eight additional textural parameters as well as the maximum and mean SUV and the TLG showed significance. A statistically significant correlation between the change of maximum SUV in the course of treatment and the pretherapeutic parameters was found in both treatment groups for three textural features. In patients with malignant melanoma textural parameters in pretherapeutic FDG-PET/CT examinations seem to have prognostic power for treatment response of immunotherapy with vemurafenib and ipilimumab. This can be an important step towards personalized tumor therapy.

Utility of FDG-PET/CT in Patients with Advanced Renal Cell Carcinoma with Osseous Metastases: Comparison with CT and 99mTc-MDP Bone Scan in a Prospective Clinical Trial

Objective: Compare FDG-PET/CT, CT, and bone scan for detecting and monitoring bone metastases’ response in metastatic renal cell cancer (mRCC). Methods: Patients with mRCC prospectively underwent FDG-PET/CT, CT, and bone scans at baseline and after 8 weeks of therapy. Tumor visibility and metabolic activity were retrospectively recorded. Response was evaluated by PERCIST, RECIST, and MD Anderson bone criteria. Kaplan-Meier methodology estimated event-time distributions for PFS, OS, and time to symptomatic skeletal event (SSE). Log-rank test tested differences in event-time distributions between response at 8 weeks by response criteria. Results: Sixteen patients (n = 30; 53%) were evaluable. Baseline FDG-PET/CT detected more osseous metastases (n = 55) than CT (n = 45) or bone scan (n = 34). From baseline to 8 weeks, metabolic activity of lesions decreased >20%, while qualitative and quantitative CT and bone scan parameters were unchanged for most patients. Partial metabolic responders by PERCIST had longer PFS and OS (n = 5, 20+ months) versus those with stable (n = 9; PFS = 9.2 mos, OS = 8.7 mos) and progressive (n = 2; PFS = 5.4 mos, OS = 12.1 mos) metabolic disease, p = 0.09 and 0.42, respectively. By RECIST, longer PFS and OS was seen for stable (n = 12, PFS = 8.3 mos, OS = 17.7 mos) versus progressive (n = 4; PFS = 3.7 mos, OS = 7.5 mos) disease, p = 0.16, 0.02, respectively. OS was not reached, but estimated ≥20 mos, for 4 patients with RECIST SD and PERCIST PMR, compared to OS of 17.7 mos for other patients with RECIST SD. Conclusions: FDG-PET/CT identified more bone metastases and greater numbers of quantitative and qualitative treatment responses in mRCC compared to CT and bone scan. FDG-PET/CT also may identify a sub-group of patients with better outcomes than predicted by standard imaging modalities.

Clinical utility of 177 Lu-DOTATATE PRRT in somatostatin receptor-positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity.

The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor-positive metastatic medullary thyroid carcinoma (MTC), including progression-free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients. A total of 43 somatostatin receptor-positive metastatic MTC patients, treated with 177 Lu-DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post-treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68 Ga-DOTATATE, 18 F-FDG PET-CT, CeCT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (CtnDT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI-CTCAE v5.0 criteria. The observed Kaplan-Meier curves for both PFS and OS since first PRRT were compared with CtnDT (more than 24 months vs less than 24 months) by log-rank (Mantel-Cox) test. The prognostic variables were investigated for their association with CtnDT and response to PRRT using Cox proportional-hazards model. The median OS was 26 months (95% CI 16.6-35.3 months) and the median PFS 24 months (95%.CI: 15.1-32.9 months). Following 177Lu-DOTATATE PRRT, the observed median PFS and OS was longer in patients who had CtnDT more than 24 months compared to those with CtnDT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time-point of first 177 Lu-DOTATATE PRRT cycle, the patients with CtnDT more than 24 months had a significantly longer PFS (P < .001) and OS (P < .001) compared to those with less than 24 months. Less than 5 lesions, FDG uptake in lesions (SUVmax of <5) and patients alive at the time of analysis were the significant variables for association with CtnDT (more than 24 months). Out of 43 patients, 26 were responders (61%) and 17 nonresponders (39%) based upon PERCIST criteria, and 27 were responders (62%) while 16 patients were nonresponders (38%) based upon RECIST 1.1 criteria. The univariate analysis showed significant association between responses to PRRT with following prognostic variables: (a) size of lesions (<2 cm) and (b) FDG uptake in lesions (SUVmax of <5). PRRT was well tolerated in all patients without any major grade 3 or 4 toxicity. The results demonstrated that, 177 Lu-DOTATATE is a potentially efficacious and safe therapeutic option in SSTR avid metastatic MTC patients.

PET/CT Imaging Characteristics After Radioembolization of Hepatic Metastasis from Breast Cancer.

To define positron emission tomography/computed tomography (PET/CT) imaging characteristics during follow-up of patients with metastatic breast cancer (MBC) treated with yttrium-90 (Y90) radioembolization (RE). From January 2011 to October 2017, 30 MBC patients underwent 38 Y90 glass or resin RE treatments. Pre-RE PET/CT was performed on average 51days before RE. There were 68 PET/CTs performed after treatment. Response was assessed using modified PERCIST criteria focusing on the hepatic territory treated with RE, normalizing SUVpeak to the mean SUV of liver uninvolved by tumor. An objective response (OR) was defined as a decrease in SUVpeak by at least 30%. Of the 68 post-RE scans, 6 were performed at 0-30days, 15 at 31-60days, 9 at 61-90days, 13 at 91-120days, 14 scans at 121-180days, and 11 scans at > 180days after RE. Of the 30 patients, 25 (83%) achieved OR on at least one follow-up. Median survival was 15months after the first RE administration. Highest response rates occurred at 30-90days, with over 75% of cases demonstrating OR at that time. After 180days, OR was seen in only 25%. There was a median TTP of 169days among responders. In MBC, follow-up PET/CT after RE demonstrates optimal response rates at 30-90days, with progression noted after 180days. These results help to guide the timing of imaging and also to inform patients of expected outcomes after RE.

Clinical Outcomes of Stereotactic Body Radiation Therapy for Extracranial Oligometastatic Ovarian Cancer

The purpose of this study was to evaluate the role of stereotactic body radiosurgery (SBRT) for extracranial metastases in patients with ovarian cancer. From March 2009 to June 2018, 33 patients with ovarian cancer of any histology underwent SBRT treatment of 90 extracranial lesions. All patients underwent primary surgical excision at the time of diagnosis and at least one line of chemotherapy. Median age was 63 years (range: 36-84). Dosing regimens included 6 Gy x 4 in 26 (29%), 6 Gy x 3 in 8 (9%), 10 Gy x 3 in 10 (11%), 7 Gy x 3 in 8 (9%), and 12 Gy x 3 in 7 cases (8%). The sites of disease included lymph node (46 lesions), liver (20 lesions), soft tissue (16 lesions), bone (4 lesions), spleen (2 lesions), pancreas (1 lesion), and lung (1 lesion). Response to SBRT was assessed via FDG-PET/CT using PERCIST criteria in 66 cases and via CT imaging using RECIST criteria in 24 cases. Toxicity was assessed via the RTOG/EORTC criteria. Median follow-up was 54.6 months. Imaging completed 3 months after treatment showed a complete response (CR) in 59 cases (66%), partial response (PR) in 16 cases (18%), stable disease (SD) in 13 cases (14%), and progressive disease in 2 cases (2%). Patients with nodal lesion were more likely to achieve CR when compared to liver lesions (p=0.02, 78.3% vs 55.0%) and soft tissue lesions (p= 0.046, 78.3% vs 50.0%). Local control (LC) was 80% at 5 years, and multivariate analysis revealed that achieving CR (p=0.016) correlated with improved LC. The median systemic treatment-free interval, median progression-free survival (PFS), and median overall survival (OS) were 8 months, 3.3 months, and 49.6 months, respectively. Achieving CR was associated with improved OS (p=0.001, 5-year OS 54% vs 30%) and improved PFS (p=0.014, 1-year PFS 22% vs 7%). Overall acute toxicity occurred in 27 cases (30%), and all of which were grade 1 or 2. This analysis suggests that SBRT is a well-tolerated and effective treatment option for oligometastatic ovarian cancer, providing durable local control with the potential to delay systemic treatment. Patients who achieved CR were shown to have improved LC, PFS, and OS.

Staging and Response Evaluation to Neo-Adjuvant Chemoradiation in Esophageal Cancers Using 18FDG PET/ CT with Standardized Protocol.

Background:Precise staging of esophageal cancer (EC) is important for selection of optimal treatment option and prognostication. Aim of this study was to assess the role of 18FDG PET/CT in staging and response evaluation to neoadjuvant chemoradiation (nCR) in EC patients using standardized imaging protocol. Material and methods:This prospective study was conducted at PET/CT Section of Department of Radiology, Aga Khan University Hospital Karachi, Pakistan from July 2017 till February 2018. We included 34 biopsy proven EC patients who had 18FDG PET/CT and CT of neck, chest and abdomen as part of initial staging. Eleven patients had post-nCR 18FDG PET/CT using standardized imaging protocol as per EANM guidelines. CT and PET/CT based staging was compared. Based on PERCIST criteria, response evaluation was assessed using change in highest SUVmax (%∆SUVmax) in baseline and follow-up scans (primary lesion, node or extra-nodal metastases).Results:Mean age of cohort was 57 ± 14 years (23 males and 11 females) having adenocarcinoma (AC) in 23 and squamous cell cancer (SCC) in 11 patients. Mean 18FDG dose, uptake time and hepatic SUVmean for baseline scans were 169 ±54 MBq, 65 ±10 minute and 1.91 ± 0.49 which were within ± 10%, ± 15% and ± 20% for follow-up scans in 11 patients respectively. Mean size (craniocaudal dimension in mm) and SUVmax of primary tumor was 56 ±27 mm and 13.4 ± 4.7. Based on 18FDG PET/CT findings, patients were categorized into N0 (10/34), N1 (09/34), N2 (11/34) and N3 (04/34) while 11/32 had stage IV disease. No significant difference was seen in AC and SCC groups. CT found stage IV disease in 3/34 (09%) while PET/CT found in 11/34 (32%; p value: 0.019) cases. PET/CT showed concordance with CT in 41% while discordance (all with upstaging) seen in 59%. On follow-up PET/CT, complete metabolic response was seen in 5/11 (45%) and partial metabolic response was noted in 6/11 (55% - p value non-significant) patients. Median %∆SUVmax over primary lesions was 49.84% (-32.69 -100%) while over nodal sites it was 41.18% (-82.60 -100%). Conclusion:We conclude that 18FDG PET/CT was found a sensitive tool in initial staging of EC. Compared with CT, it had higher diagnostic accuracy for distant nodal and extra-nodal metastasis. %∆SUVmax between baseline and post-nCR studies acquired with standardized protocol had changed management in more than half of our patients. For response evaluation in EC more studies with standardized 18FDG PET/CT imaging protocols are warranted.

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

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

TAC y PET/TC con 18-FDG para evaluar la respuesta al tratamiento en linfoma de Hodgkin y no Hodgkin

The assessment of lymphoma response to treatment is based on imaging studies. To correlate the assessment of lymphoma treatment response by computed tomography (CT) and by positron emission tomography/computed tomography (PET/CT). Cross-sectional, observational study, where records of patients with lymphoma under surveillance by CT and PET/CT were reviewed. The study population consisted of 43 patients with a mean age of 32.7 ± 22.4 years; 26 (60.5 %) had a diagnosis of Hodgkin's lymphoma and 17 (9.5 %) had non-Hodgkin lymphoma. By CT, 34 (79.1 %) were diagnosed with disease and nine (20.9 %) without disease. The criteria used to assess the response was radiologist experience in 39 (90.7 %) and RECIST 1.1 criteria in four (9.3 %). The diagnosis by 18-FDG PET/CT was no response to treatment or partial response-recurrence in 32 (74.4 %) and response to treatment in 11 (25.6 %); with PERCIST criteria in 13 (30.2 %) and Deuaville criteria in 30 (69.8 %). When the diagnosis by CT versus 18-FDG PET/CT was compared, out of 11 patients with complete response on PET/CT, three had a similar CT diagnosis. Of the 34 patients with data consistent disease diagnosed by CT, 26 had similar results by 18-FDG PET/CT (p = 0.54). The value of lymphoma treatment response on CT does not agree with that obtained by 18-FDG PET/CT.

The use of molecular volumetric parameters for the evaluation of Lu-177 PSMA I&T therapy response and survival.

The primary aim of this study was to evaluate the volumetric therapy response via Ga-68 PSMA I&T PET/CT in patients treated with Lu-177 PSMA I&T therapy. The secondary purpose was to determine the impact of volumetric parameter responses to overall survival. PSMA tumor volumes (PSMA-TV) and tumor lesion PSMA expressions (TL-PSMA) were calculated with a semi-automatic program on Ga-68 PSMA I&T PET/CT images that were obtained before and after Lu-177 PSMA I&T therapies with 19 patients. The median overall survival was compared with PSMA-TV, TL-PSMA, SUVmax, PSA, and alteration in PERCIST criteria. PSMA-TV values were decreased in 12 patients (63%), and TL-PSMA values were decreased in 15 patients (79%) following the therapy. The SUVmax and the PSA values were also decreased in 14 (74%) and 10 (53%) patients, respectively. The complete remission (CR) was observed in two patients (10%). The partial response (PR) and progressive disease were observed in 6 (32%) and 11 (58%) patients, respectively, according to PRECIST criteria. The survival rates were statistically significant in patients with a decrease in PSMA-TV and TL-PSMA values than patients without any decrease (p 0.001, p < 0.001, respectively). However, the survival rates did not differ in responders (PR or CR) and non-responders according to the PERCIST criteria (p 0.232). The survival rates did not also differ in responders and non-responders according to the SUVmax and PSA values (p 0.140, p 0.206, respectively). Molecular and volumetric parameters are beneficial in the assessment of Lu-177 PSMA I&T therapy response. Although the number of patients is small, TL-PSMA response, which includes both the tumor volume and PSMA expression in tumor, may be considered as the most valuable parameter for the evaluation of the therapy response and the prediction of survival rate.

Abstract PD4-12: Use of 64Cu-DOTA-trastuzumab positron emission tomography (PET) to predict response to ado-trastuzumab emtansine (TDM1)

Abstract Background: We have demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive breast cancer and are now seeking to evaluate the methodology for prediction of response and benefit to ado-trastuzumab emtansine (TDM1) in women with metastatic disease. Methods: Patients with metastatic breast cancer were eligible if they had biopsy confirmed HER2 + disease, at least 1 site of metastasis 2.0 cm or larger outside the biopsy site, and were to receive TDM1 as therapy. Pretreatment staging included 18F-FDG/PET. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 21-25 h and 47-48 h over fields of view chosen in reference to 18F-FDG scans. TDM1 was administered at a dose of 3.6 mg/kg every 3 weeks. Restaging 18F-FDG/PET was performed every 2 cycles, and response to therapy was determined by PERCIST criteria. The radiolabel uptake was measured in terms of maximum voxel standardized uptake value (SUVmax). Results: Ten women enrolled on study and are evaluable for response; three continue on TDM1 for 22-40 months and four patients remained on treatment for at least 1 year. The median age was 54.5 years (48-83 years); seven received prior trastuzumab-containing chemotherapy 3 wks to 55 months prior to study entry. HER2 was positive by IHC in 5 and by FISH in 5 (3 were 2+ by IHC; 1 was 1+ and 1 indeterminate). Complete or partial metabolic response was observed in 5 patients. Patients had their average SUVmax on 64Cu-DOTA trastuzumab PET (aSUVmax) assessed in addition to individual assessments on up to 8 lesions on both Day1 and Day2. The mean aSUVmax was (6.3, 8.8) for responding patients and (4.4, 5.2) for non-responder (day1, day2). The difference between responders and non-responders on Day1 aSUVmax was marginally significant (p=0.06), but significant on Day2 (p=0.04). The three highest aSUVmax on both day1 and day2 were three of the four patients with PFS&amp;gt;1 year. Data on the relationship of 64Cu-DOTA trastuzumab PET to IHC and FISH, and individual lesion SUVmax including evidence suggesting a potential threshold effect will be presented. Conclusions: In women with biopsy confirmed HER2 positive metastatic disease, 64Cu-DOTA-trastuzumab PET imaging is predictive for response to TDM1. Citation Format: Mortimer JE, Bading JR, Frankel P, Tumyan L, Tran TT, Rockne RC, Shively JE, Gidwaney N, Park J, Colcher DM. Use of 64Cu-DOTA-trastuzumab positron emission tomography (PET) to predict response to ado-trastuzumab emtansine (TDM1) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-12.

68Ga-PSMA PET/CT for monitoring response to 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer.

To evaluate the use of 68Ga-PSMA PET/CT for monitoring response to 177Lu-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC). Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with 177Lu-PSMA-617 and whose records included 68Ga-PSMA PET/CT imaging before the first and after the third or fourth treatment cycle. A treatment response based on 68Ga-PSMA PET/CT was defined according to a modified version of the PERCIST criteria. A decline in PSA level of ≥50% was considered the reference standard. The sensitivity, specificity, positive and negative predictive values, and ROC curves were calculated, and patient survival times in relation to the PET results were also analysed. 68Ga-PSMA PET/CT had a sensitivity of about 85% and a specificity of between 55% and 65%. The negative and positive predictive values ranged between 70% and 78%. The fitted ROC area was 0.70. The survival time was about 19.6months in patients with a treatment response, while nonresponders had a survival time of about 15.9months. However, this difference between the groups was not statistically significant. Our results indicate that 68Ga-PSMA PET/CT could be a useful tool for the evaluation of response to 177Lu-PSMA-617 radioligand therapy within a theranostic framework.

Evaluation of response in patients of metastatic castration resistant prostate cancer undergoing systemic radiotherapy with lutetium177-prostate-specific membrane antigen: A comparison between response evaluation criteria in solid tumors, positron-emission tomography response criteria in solid tumors, European organization for research and treatment of cancer, and MDA criteria assessed by gallium 68-prostate-specific membrane antigen positron-emission tomography-computed tomography.

Introduction:We evaluated various morphological and molecular response criteria in metastatic castration-resistant prostate cancer (PCa) patient undergoing peptide receptor radioligand therapy (PRLT) with Lutetium177-prostate-specific membrane antigen (PSMA) by using Gallium 68-PSMA positron-emission tomography-computed tomography (Ga68-PSMA PET-CT).Methods:A total of 46 pre- and 8–12 weeks’ post-PRLT Ga68-PSMA PET-CT studies were reanalyzed (23 comparisons). Prostate-specific antigen drop of ≥50% and ≥25% increase was considered as partial response (PR) and progressive disease (PD), respectively, for biochemical response (BR) while change in-between was considered as stable disease (SD). Response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and MD Anderson (MDA) criteria for morphological response while PET response criteria in solid tumors 1.0 (PERCIST 1.0) and European organization for research and treatment of cancer (EORTC) criteria for molecular response were used. Kappa coefficient was derived to see the level of agreement.Results:The proportion of PD, PR, and SD by BR and RECIST criteria was 9 (39.13%), 3 (13.04%), and 11 (47.83%) and 5 (21.74%), 2 (8.70%), and 16 (69.57%), respectively. The proportion of PD, PR, and SD was same by PERCIST and EORTC criteria and which were 8 (34.78%), 5 (21.74%), and 10 (43.48%). The proportion of PD, PR, and SD by MDA criteria was 1 (4.35%), 1 (4.35%), and 21 (91.30%), respectively. Poor agreement between BR and both morphological criteria while a statistically significant agreement with both molecular criteria seen.Conclusion:We concluded that molecular criteria performed better than morphological criteria in response assessment by Ga68-PSMA PET-CT in metastatic castration resistant PCa patients undergoing PRLT.

Impact of PET reconstruction protocols on quantification of lesions that fulfil the PERCIST lesion inclusion criteria

BackgroundThe aim of this study was to compare liver and oncologic lesion standardized uptake values (SUV) obtained through two different reconstruction protocols, GE’s newest clinical lesion detection protocol (Q.Clear) and the EANM Research Ltd (EARL) harmonization protocol, and to assess the clinical relevance of potential differences and possible implications for daily clinical practice using the PERCIST lesional inclusion criteria.NEMA phantom recovery coefficients (RC) and SUV normalized for lean body mass (LBM), referred to as SUV normalized for LBM (SUL), of liver and lesion volumes of interest were compared between the two reconstruction protocols. Head-to-toe PET/CT examinations and raw data from 64 patients were retrospectively retrieved. PET image reconstruction was carried out twice: once optimized for quantification, complying with EARL accreditation requirements, and once optimized for lesion detection, according to GE’s Q.Clear reconstruction settings.ResultsThe two reconstruction protocols showed different NEMA phantom RC values for different sphere sizes. Q.Clear values were always highest and exceeded the EARL accreditation maximum for smaller spheres. Comparison of liver SULmean showed a statistically significant but clinically irrelevant difference between both protocols. Comparison of lesion SULpeak and SULmax showed a statistically significant, and clinically relevant, difference of 1.64 and 4.57, respectively.ConclusionsFor treatment response assessment using PERCIST criteria, the harmonization reconstruction protocol should be used as the lesion detection reconstruction protocol using resolution recovery systematically overestimates true SUL values.

99. Absorbed dose correlates with metabolic response to radioembolization of liver metastases with resin 90Y-microspheres

Purpose To investigate possible correlation between absorbed dose (AD) and tumour response by means of Tumour Control Probability (TCP) in liver metastases treated with radioembolization (RE) with resin 90Y-microspheres. To assess response, the analysis of parameters from FDG-PET/CT has been preferred to RECIST criteria as metabolic response has proven to anticipate morphologic response. Methods Patients with chemo-refractory liver metastases from solid tumours scheduled to receive RE underwent FDG-PET/CT scan before and 6 weeks after RE. 99mTc-MAA (75–111 MBq) were injected 2 weeks before RE to perform dosimetry based on SPECT fused to contrast CT. Response assessment was based on PERCIST criteria. Variation (%) of PET parameters versus basal examination were evaluated to establish Complete-Response (CR), Partial-Response (PR), Stable-Disease (SD), Progressive-Disease (PD). Results 22 patients with hepatic lesions from colon-rectal (11), breast (7), ovary (1), endometrial (1), parotid (1) cancer, cholangiocarcinoma (1) were suitable for analysis. All patients received a single RE treatment (median activity: 1.7 GBq; range: 0.6–2.9 GBq). Median (range) tumour AD: 100(30–443) Gy. Metabolic response rate of lesions based on PERCIST were: CR = 31%; PR = 28%; SD = 24%; PD = 17%. Two different TCP curves were obtained by probit regression when considering: i) endpoint-1: PR or CR; ii) endpoint-2: CR only (p = 220 Gy only CR were observed. TCP of 50%, 75%, 100% were obtained at: i) 108, 120, 165 Gy; ii) 135, 160, 225 Gy. Conclusions Despite the variety of primary tumours, relatively low cohort of patients, and uncertainty of dosimetry with 99mTc-MAA, our preliminary data provided evidence of correlation between response based on PET/CT and AD. These encouraging results need to be confirmed with more ample dataset and, possibly, tumour type differentiation. Other PET/CT parameters such as the metabolic tumour volume and tumour lesion glycolysis are being considered for comparison with PERCIST and possible improved correlations.

Effects of Tumor Burden on Reference Tissue Standardized Uptake for PET Imaging: Modification of PERCIST Criteria.

Purpose To examine the effect metabolic burden (tumor and/or cardiac myocyte uptake) has on fluorine 18 fluorodeoxyglucose (FDG) distribution in organs and tissues of interest. Materials and Methods Positron emission tomographic (PET)/computed tomographic (CT) scans at the Ann Arbor Veterans Affairs hospital from January to July 2015 were reviewed. A total of 107 scans (50 patients; mean age, 64.3 years ± 13.2 [standard deviation]) had metabolic tissue burden assessed by using total lesion glycolysis (TLG) obtained from autosegmentation of the tumor and/or cardiac tissue. Standardized uptake value (SUV) and subsequent normalized SUV uptake in target organs and tissues were compared with 436 FDG PET/CT scans previously reported in 229 patients as a function of TLG to describe the effect(s) that metabolic burden has on reference tissue (blood pool, liver, and brain) FDG uptake. Subsequent regression by using linear mixed-effects models was used. If the slope of the regression was significantly (P < .05) different than zero, then an effect from TLG was present. Results There was a negative inverse relationship (P < .0001) between FDG uptake within reference tissues (blood pool, liver, and brain) and TLG in comparison to the study population at similar blood glucose levels. This TLG effect was no longer statistically significant (P > .05) when FDG uptake was normalized to a reference tissue (eg, blood pool or liver). Conclusion Metabolic tissue burden can have a significant effect on SUV measurements for PET imaging. This effect can be mitigated by normalizing FDG uptake to a reference tissue. © RSNA, 2018.

Oligometastases in prostate cancer

BackgroundProstate-specific membrane antigen positron emission tomography/computed tomography (PSMAPET/CT) is a new and evolving diagnostic method in prostate cancer with special impact on treatment planning in image-guided radiotherapy (IGRT). Initial results of metabolic response in repeated PSMA PET/CTs after hypofractionated IGRT for metastatic lesions are reported here.Materials and methodsOf 280 patients investigated with 68Ga-PSMA PET/CT in the period from 01/2014 through 12/2016 in the authors’ department, patients were selected according to the following criteria: oligometastatic disease at initial PSMA PET/CT defined as not more than five metastatic lesions, hypofractionated IGRT to all lesions, no systemic therapy in the last 6 months and during follow-up, and at least one follow-up PSMA PET after radiotherapy. Radiotherapy was administered to all PSMA PET-detected lesions (CTV = PET-GTV + 1 to 2 mm), mostly with 35 Gy in five fractions (one lesion with four fractions of 7 Gy due to dose constraints, two lymph nodes with 50 Gy in 25 fractions to an extended volume plus a boost of 7 Gy × 2 to the PET-positive volume). Metabolic response of irradiated lesions was evaluated on repeated PSMA PET/CTs according to PERCIST criteria. Five patients with a total number of 12 PSMA PETs matched the criteria. Patients received radiotherapy to all PET-positive lesions and had at least one (in one case three) follow-up PSMA PET examinations after radiotherapy with an interval to the first PET of 2–15 months; the median follow-up for all patients was 11 months.ResultsThe mean prostate-specific antigen (PSA) values at the time of examination were 8.9 ± 8.5 ng/ml (median 3.3 ng/ml, range 0.17–21.8 ng/ml). A total number of 18 metastatic deposits were detected. The PET-positive tumor volume was 5.9 ± 13.3 cm3 (median 1.25 cm3). The mean standardized uptake value (mean SUVmax) of the 18 metastatic lesions decreased from 19.9 ± 23.3 (mean ± SD) prior to RT to 5.4 ± 4.6 at post-radiotherapy PSMA PET/CT. Using PERCIST criteria, 14 lesions (78%) showed a metabolic response in PSMA PET with a reduction of SUV of at least 30%, as well as a significant decrease in lesion size; in seven of these lesions, no uptake of 68Ga-PSMA was detectable. In follow-up PET scans, only two lesions showed metabolic progression with an increase in SUVmax yielding a local progression-free survival of 88% after 1 year. There was a correlation between the time interval after radiotherapy (median 3 months, range 1–9 months) and response (p = 0.04) with better metabolic response after longer follow-up.ConclusionsPreliminary results of this study show high metabolic response rates of PSMA PET-positive metastatic lesions after hypofractionated radiotherapy in follow-up PSMA PET with promising local control rates. An interval of several months may be required to fully estimate the efficacy of radiotherapy in control PSMA PET.

MA 17.12 Comparison of EORTC, PERCIST, PeterMac & Deauville PET Response Criteria after Radical ChemoRT in Non-Small-Cell Lung Cancer

MA 17.12 Comparison of EORTC, PERCIST, PeterMac & Deauville PET Response Criteria after Radical ChemoRT in Non-Small-Cell Lung Cancer

P3.13-016 18F-FDG-PET/CT for Prediction of Survival after Induction Chemotherapy in Locally Advanced NSCLC – a Comparison of Methods

In patients with inoperable, locally advanced NSCLC, radical chemo-radiotherapy is the preferred treatment, and 18F-FDG-PET/CT is increasingly used for radiotherapy planning. Despite the introduction of the PERCIST criteria for evaluation of response with 18F-FDG-PET/CT, various methods are being used making comparisons of studies a difficult task. The aim of this study was to investigate which method for analyzes of 18F-FDG-PET/CT provided the best prediction of survival.

64Cu-DOTA-trastuzumab PET/CT to predict response to ado-trastuzumab emtansine (TDM1) in HER2-positive metastatic breast cancer.

e12525 Background: Having demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive (HER2+) breast cancer, we now evaluate the methodology for prediction of response and benefit from TDM1 in women with metastatic disease. Methods: Patients eligible to receive TDM1 as therapy were chosen on the basis of biopsy confirmed HER2+ disease, and at least 1 site of metastasis ≥ 2.0 cm outside the biopsy site. Pretreatment staging included 18F-FDG PET/CT. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 16-28 h (Day1) and 39-49 h (Day 2) over fields of view chosen in reference to the 18F-FDG scans. TDM1 (3.6 mg/kg) was administered every 3 weeks. Restaging 18F-FDG PET/CT was performed every 2 cycles, and response to therapy was determined by PERCIST (solid tumor) criteria. Radiolabel uptake was measured in terms of maximum voxel, standardized uptake value (SUVmax). Results: Ten women between the ages of 48-83 years old (median 55 years) qualified for study, and have been evaluated for response; 4 continue on TDM1 with treatment durations of 3-27 months.Three were trastuzumab-naïve, while 7 had received trastuzumab-containing chemotherapy 3 wks to 55 mo prior to study entry. HER2 was positive by ImmunoHistoChemistry, IHC (3+) in 5 patients, and by FISH testing in the other 5 (3 were 2+ by IHC; 1 was 1+, and 1 was indeterminate). Complete or partial metabolic response was observed in 5 patients. Median Day 2 SUVmax for 64Cu-DOTA trastuzumab was 9.3 g/ml in responding patients, and 4.6 g/ml in non-responders ( P= 0.03). Progression-free survival was longer for patients with higher SUVmax, with a hazard ratio of 0.73 (95% confidence interval 0.46-1.16) for each 1 unit increase in SUVmax. This was not statistically significant, although we can select a threshold SUVmaxfor which the effect is significant even for this small study. Further data is required to confirm such a threshold effect. Conclusions: 64Cu-DOTA-trastuzumab PET imaging predicts benefit from TDM1 in women with biopsy-confirmed HER2+ metastatic disease. Supported by NCI Clinical trial information: NCT02827877.