11:21 CET
111 - e-Poster Presentation Session 1 - Oncology: Oncology - Greatest Hits!
Clinical Oncology Basic Oncology Radionuclide Therapy & Dosimetry Artificial intelligence and Radiomics
Sunday, October 13, 08:00 - 09:30
Room: Room 133/134
Type of session: e-Poster Presentation Session
Topic: Clinical Oncology, Basic Oncology, Radionuclide Therapy & Dosimetry, Artificial intelligence and Radiomics
Sub topic: 717 Imaging Guided Surgery (incl. Sentinel Lymph Node), 709 Urogenital, 719 Therapy Response Assessment, 604 Animal Models, 806 Local Radionuclide Treatment, 704 Breast, 710 Gynaecological, 711 Lymphoma, 712 Leukaemia & Myeloma, 705 Lung, 107 Miscellaneous
Chairpersons: N. Manevska (Skopje/MK), V. Prasad (Bad Berka/DE)

16 presentations in this session:
Visualization of sentinel lymph nodes in gynecological cancer patients
I. Sinilkin1, V. Chernov1, A. Medvedeva1, R. Zelchan1, O. Bragina1, A. Chernyshova1, L. Kolomiets1, M. Ochirov1, E. Stasyuk2, V. Skuridin2;
1Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, RUSSIAN FEDERATION, 2Tomsk Polytechnic University, Tomsk, RUSSIAN FEDERATION.

Aim/Introduction: To evaluate the diagnostic efficacy of a new radiopharmaceutical 99mTc- aluminum gammoxide for the detection of sentinel lymph nodes (SLN) in gynecological cancer patients. Materials and Methods: The study included 60 patients with endometrial cancer T1a-bNxM0 (n = 30) and cervical cancer T1a-bNxM0 (n = 30). The day before the operation, 2-4 submucosal injections of 99mTc-Alotech at a dose of 20 MBq per injection site were made to the cervix. Patients underwent single photon emission computed tomography (SPECT) of the pelvic region 18 hours after administration of the radiocolloid. Evaluation of the results of the study was carried out both visually and the intensity of the radiopharmaceutical uptake in the SLN was compared with the injection site. To improve the topographic localization of the sentinel lymph nodes, a multimodal technique was used, consisting in combining the results of the SPECT and MRI. Radioguide intraoperative detection of sentinel lymph nodes using a gamma probe was carried out. After removal of the sentinel lymph nodes, pelvic lymph node dissection was performed to examine the condition of the remaining lymph nodes. Results: Sentinel lymph nodes were detected in all patients by SPECT and radioguide mapping. In three (5%) cases one SLN were found, in 57 (95%) patients - 2 bilateral SLN were visualized. In 78.3% of cases SLN were located in the region of the external and internal iliac vessels, and in all cases the location of the SLN was determined by SPECT/MRI study. The excised SLNs were evaluated by urgent cytology with subsequent routine histological examination. By urgent cytology in 9 SLN metastatic lesions were and two patients had micrometastases. Conclusion: The use of radiopharmaceutical 99mTc- aluminum gammoxide in patients with gynecological cancer allows you to identify SLN with sensitivity and specificity of 100%. The use of the multimodal SPECT/MRI fusion allows accurately indicate the anatomical localization of the SLN. References: none

Evaluation of PSMA Expression Changes on PET/CT Before and After Initiation of Novel Antiandrogen Drugs (Enzalutamide or Abiraterone) in Metastatic Castration-Resistant Prostate Cancer Patients
N. Plouznikoff1,2, C. Artigas1, S. Sideris3, T. Gil3, N. Martinez-Chanza3, T. Roumeguere4, A. Peltier5, P. Flamen1;
1Department of Nuclear Medicine, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, BELGIUM, 2Department of Nuclear Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, CANADA, 3Department of Oncology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, BELGIUM, 4Department of Urology, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, BELGIUM, 5Department of Urology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, BELGIUM.

Aim/Introduction: Novel androgen deprivation therapies are currently indicated for castration-resistant prostate cancer patients. The aim of this study was to retrospectively investigate the association between 68Ga-labeled Prostate-Specific Membrane Antigen (PSMA) expression changes on PET/CT and the response to treatment, mainly based on Prostate-Specific Antigen (PSA) levels, following the start of enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) patients. Materials and Methods: We retrospectively reviewed all 68Ga-PSMA-11 PET/CT scans performed at our institution from November 2014 to March 2019. We included mCRPC patients with a first 68Ga-PSMA PET/CT performed <2 months before the start of enzalutamide or abiraterone, and a second 68Ga-PSMA PET/CT performed <1 year after (with no modification in therapy between scans). 11 and 15 patients were included in the enzalutamide and abiraterone arms, respectively. All associated clinical records were reviewed. The biological data was used to distinguish PSA-non-responders (increasing PSA following the start of therapy or the nadir thereafter) and PSA-responders (decreasing PSA following the start of therapy or the peak thereafter). The PSMA PET/CT response was assessed visually by two independent nuclear medicine physicians. Patients were classified as PSMA-non-responders (≥1 new PSMA-expressing metastases, majority of PSMA-expressing metastases increasing in intensity, or stable PSMA-expression of the disease) or PSMA-responders (complete disappearance of pathologic PSMA uptake, or majority of PSMA-expressing metastases decreasing in intensity). Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. Results: For enzalutamide and abiraterone, the median delay between the first 68Ga-PSMA PET/CT and the start of therapy was 8 (IQR:7-16) and 24 (IQR:8-30) days, respectively. The median delay between the start of therapy and the second 68Ga-PSMA PET/CT was 110 (IQR:76-124) and 87 (IQR:71-242) days, respectively. PSA-response and PSMA-response were perfectly associated for both enzalutamide (8 PSA/8 PSMA-non-responders, 3 PSA/3 PSMA-responders; p=0.006, Phi=1.000) and abiraterone (11 PSA/11 PSMA-non-responders, 4 PSA/4 PSMA-responders; p=0.001, Phi=1.000). No isolated PSMA flare was detected, as PSA-response was always associated with a decrease in PSMA-expression on the second PET/CT. Conclusion: This retrospective study suggests that, after a median follow up of 3 months under enzalutamide or abiraterone, PSMA expression changes on PET/CT are strongly associated with PSA response. No PSMA-expression flare was found, but an early and limited flare phenomenon cannot be excluded. Prospective studies are needed to better understand PSMA expression dynamics following the start of enzalutamide and abiraterone, along with its potential role in response assessment. References: None.

Neoadjuvant Pazopanib Treatment In High-risk Soft Tissue Sarcoma: A Quantitative Dynamic 18F-FDG PET/CT Study Of The German Interdisciplinary Sarcoma Group
C. Sachpekidis1,2, I. Karampinis3, J. Jakob4, B. Kasper5, K. Nowak6,7, L. Pilz8, U. Attenberger9, T. Gaiser10, H. G. Derigs11, M. Schwarzbach12, P. Hohenberger3, A. Dimitrakopoulou-Strauss1, U. Ronellenfitsch3,13;
1Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, GERMANY, 2Nuclear Medicine Dept, Bern University Hospital, Bern, SWITZERLAND, 3Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Mannheim, GERMANY, 4Department of General, Visceral and Child Surgery, University Medical Center Göttingen, Göttingen, GERMANY, 5Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Mannheim University Medical Center, Mannheim, GERMANY, 6Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Heidelberg, GERMANY, 7Department of Abdominal, Vascular and Thoracic Surgery, Romed Klinikum, Rosenheim, AUSTRIA, 8Medical Faculty Mannheim, University of Heidelberg, Mannheim, GERMANY, 9Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim, GERMANY, 10Institute of Pathology, University Medical Center Mannheim, Mannheim, GERMANY, 11Department of Hematology and Oncology, Klinikum Frankfurt-Hoechst, Frankfurt am Main, GERMANY, 12Department of Surgery, Klinikum Frankfurt-Hoechst, Frankfurt am Main, GERMANY, 13Department of Abdominal, Vascular, and Endocrine Surgery, University Hospital Halle, Halle (Saale), GERMANY.

Aim/Introduction: The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for treatment of metastatic STS. Most recently, the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial has shown that preoperative pazopanib therapy is not effective for unselected high-risk STS, using metabolic response in 18F-FDG PET/CT as primary endpoint; nevertheless, relevant treatment effects were observed in selected patients. Herein, we evaluate the potential role of kinetic analysis of 18F-FDG data derived from application of dynamic PET/CT in response assessment to pazopanib of STS patients scheduled for surgical resection. Materials and Methods: Sixteen STS patients treated with pazopanib as neoadjuvant therapy before surgery were enrolled in the analysis. All patients underwent dynamic PET/CT prior to and after pazopanib treatment. Data analysis consisted of visual (qualitative) analysis of the PET/CT scans, semi-quantitative evaluation based on SUV calculations, and quantitative analysis of the dynamic 18F-FDG PET data based on two-tissue compartment modeling as well as on a non-compartmental model based on the calculation of the fractal dimension of the time-activity curves. Resection specimens were histopathologically assessed and the percentage of regression grade was recorded. Time to tumor relapse/progression was also calculated. Results: In the follow up 12/16 patients (75%) were alive without relapse, while four patients (25%) relapsed, among them one patient who died. Mean histopathological regression was 26%. The studied population was dichotomized according to mean value of the percentage of histopathological regression after pazopanib as a cutoff. Using the 30% regression grade as threshold, 6/14 patients (43%) showed partial remission (PR), while stable disease (SD) was seen in the rest of 8 evaluable patients (57%). Although semi-quantitative evaluation showed no statistically significant change of SUVaverage and SUVmax, 18F-FDG kinetic analysis revealed a significant decrease of the perfusion-related parameter K1. The dichotomization of the studied population according to histopathologic regression grade showed no statistically significant differences between the PR and SD groups. Conclusion: Although the widely used PET parameter SUV did not show significant response, the perfusion-related kinetic parameter K1 -reflecting the carrier-mediated transport of 18F-FDG from plasma to tumor- significantly decreased as a marker of response to pazopanib in STS. This finding could be due to the anti-angiogenic effect of pazopanib. 18F-FDG PET parameters did not show any association to histopathological regression as response to the treatment. References: None.

Role of Metabolic Response by 18F-FDG PET/CT Added to iRECIST in NSCLC Patients Treated with Immune Checkpoint Inhibitors
A. Castello1, L. Toschi2, S. Rossi2, E. Mazziotti1, E. Lopci1;
1Nuclear Medicine, Humanitas Clinical and Research Hospital - IRCCS, Rozzano (MI), ITALY, 2Oncology and Hematology, Humanitas Clinical and Research Hospital - IRCCS, Rozzano (MI), ITALY.

Aim/Introduction: To investigate the role of metabolic response with 18F-FDG PET/CT in patients with non-small cell lung carcinoma (NSCLC) treated with Immune Checkpoint Inhibitors (ICI). Materials and Methods: The trial was registered at http://www.clinicaltrials.gov (NCT03563482). We analyzed data from 25 patients (16 male, 9 female, mean age 75) with NSCLC treated with ICI prospectively enrolled from April 2017 to December 2018. 18F-FDG PET/CT and contract enhanced CT were performed at baseline and after 8 week of treatment in all patients. Response assessment was evaluated according metabolic and morphological criteria based on EORTC and iRECIST, respectively. As metabolic parameters, we utilized also metabolic tumor volume (MTV), total lesion glycolysis (TLG), as well as their percentage changes (ΔSUVmax, ΔMTV, and ΔTLG ). With a median follow-up of 11.3 months, response criteria we mutually compared and correlated to progression-free survival (PFS). Results: Based on metabolic response, after 8 weeks of ICI we identified 8 (32%) partial metabolic response (PMR), 11 (44%) stable metabolic disease (SMD), and 6 (24%) progressive metabolic disease (PMD). Median values for the other metabolic parameters resulted ΔSUVmax=+8.21%, ΔMTV=+67.7% and ΔTLG=+37.6%. On the other hand, 5 (20%) partial response (PR), 11 (44%) stable disease (SD), and 9 (36%) progressive disease (PD) were identified according to morphological criteria. On log rank test, EORTC response classified as PMR vs SMD/PMD resulted significantly correlated to PFS (p=0.014). Univariate analysis with Cox proportional hazards determined a statistically significant association to PFS also for ΔSUVmax (p=0.009), ΔMTV (p=0.03), and ΔTLG (p=0.013). Moreover, in patients with PR and SD according to iRECIST, there was a significant difference in PFS based on metabolic response (median not reached for PMR vs 6 months for SMD/PMD, p=0.023; HR 0.229). Conclusion: Metabolic response by 18F-FDG PET/CT allows for the prediction of patients with longer PFS during therapy with ICI. The added value of EORTC criteria is confirmed for patients presenting with a PR or SD according to iRECIST.
The Italian Association for Research on Cancer (AIRC - Associazione Italiana per la Ricerca sul Cancro) is acknowledged for the support on research. References: none

The evaluation of tumor response to neoadjuvant chemotherapy for esophageal cancer using PERCIST 1.0-multicenter study
H. Kaida1, K. Kitajima2, M. Nakajo3, M. Ishibashi4, R. Minamimoto5, K. Hirata6, K. Nakatani7, T. Yasuda1, K. Ishii1;
1Kindai University Faculty of Medicine, Osaka-Sayama, JAPAN, 2Hyogo College of Medicine, Nishinomiya, JAPAN, 3Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JAPAN, 4School of Medicine, Tottori University, Yonago, JAPAN, 5National Center for Global Health and Medicine, Tokyo, JAPAN, 6Hokkaido University Graduate School of Medicine, Sapporo, JAPAN, 7Kurashiki Central Hospital, Kurashki, JAPAN.

Aim/Introduction: To evaluate tumor response to neoadjuvant chemotherapy (NAC) and predict esophageal squamous cell carcinoma recurrence using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0. Materials and Methods: Our study population was collected from seven institutions in Japan, and comprised of 180 patients (153 men and 27 women) who underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and after NAC prior to planned surgical resection. The median age of our population was 66 (range, 38-78) years. Patients were divided into responder and non-responder based on pathological response, and the pathological response of both primary tumor and lymph node metastasis was evaluated. The PET parameters including peak standardized uptake value corrected for lean body mass (SULpeak) and total lesion glycolysis (TLG) were measured to evaluate PERCIST to both primary lesion and lymph node metastasis. To examine the diagnostic performance of each parameter in discriminating pathological responder, receiver operating curve (ROC) analysis was conducted, and the best cut-off point in each parameter was determined. The difference between responder and non-responder about PET parameters and clinicopathological variables was investigated using the Mann-Whitney U, Chi-squared or Fisher’s exact test. The Cox proportional hazard model was used to evaluate the effects of PET parameters and clinicopathological variables for progression free survival (PFS). Survival curves were drawn using the Kaplan-Meier method and the significant difference between survival curves was tested with the log-rank test. Results: Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) were seen in 31 101, 40, and 8 patients, respectively. Seventy-nine (43.9%) of 180 patients showed pathologic responder. An optimal percent decrease in SULpeak of 52.2% was found to have a sensitivity of 87.3%, and accuracy of 68.9%, and that of TLG of 87.3% did a sensitivity of 84.8%, specificity of 59.4%, and accuracy of 70.6%. There was a significant correlation between pathologic response and PERCIST (P<0.001). Eighty-three (46.1%) of the 180 patients developed recurrent disease. Multivaraite Cox regression analysis showed that PERCIST, %SULpeak reduction rate, number of pathological lymph nodes, and resection level were significantly associated with longer PFS (PERCIST; HR=2.134; P=0.03, %SULpeak reduction rate; HR=1.025; P<0.001, number of pathological lymph nodes: HR=2.370; P=0.001, resection level: HR=0.235; P<0.001). Conclusion: PERCIST 1.0 may be useful for predicting pathological response and prognosis after NAC in esophageal squamous cell carcinoma patients. References: none

18F-FDG PET/CT metabolic/volumetric parameters evaluation to predict response to neoadjuvant chemotherapy (NAC) and prognostic value in patients withTriple-Negative breast cancer (TNBC)
G. Paone1, S. Di Lascio2, F. Quattrocchi3, T. Ruberto1, G. Treglia1, L. Ceriani1, L. Giovanella1;
1Department of Nuclear Medicine and PET/CT Centre, Imaging Institute of Southern Switzerland, Lugano-Bellinzona, SWITZERLAND, 2Department of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, SWITZERLAND, 3Department of Nuclear Medicine, University of Messina, Messina, ITALY.

Aim/Introduction: The aim of this study was to assess response to NAC and prognostic value considering dynamic evolution of metabolic/volumetric parameters measured on 18F-FDG PET/CT in TNBC. Materials and Methods: We retrospectively analyzed 42 patients with TNBC, who performed a staging PET/CT before and after neo-adjuvant chemotherapy. Treatment-related changes in SUVmax, MTV and TLG were evaluated (ΔSUVmax, ΔMTV and ΔTLG) in the primary tumor. To identify the optimal cut-off value of these parameters a receiver-operating curve analysis was performed. Kaplan-Meier method was used to evaluate prognostic value. The associations between early metabolic/volumetric changes, pathological complete response (pCR), and event-free survival (EFS) were examined Results: Of the 42 patients, 10 (24%) achieved pCR, 14 (33%) relapsed and 10 of them died (median FU, 33 mo). No relapse was observed in patients with pCR (0.001). An optimal percent of decrease in SUVmax (cutoff value ΔSUVmax 86%, p 0.0001), MTV (cutoff value ΔMTV 99%, p 0.0001) and TLG (cutoff value ΔTLG 99%, p 0.0001) had the best predictive value in terms of pCR. No significant correlation was found with SUVmax, MTV and TLG absolute value. ΔSUVmax 84% (p 0.0026), ΔMTV 59% (p 0.0014) and ΔTLG 70% (p 0.0026) were significantly associated with EFS yielding the best prediction of recurrence Conclusion: Our data suggest that only the dynamic variation of 18F-FDG PET/CT metabolic/volumetric parameters is a predictive marker for pCR and EFS following NAC in TNBC. In the future, this could be a further tool to evaluate the response to NAC addressing to different therapeutic strategies References: None

18F-5-FPN: A Strikingly Fascinating and Potential Probe for Monitoring Photothermal Therapy Response in Malignant Melanoma
X. Lan, Y. Wang, Y. Zhang, R. An;
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, CHINA.

Aim/Introduction: The increasing global burden and the markedly breakthroughs in therapy of malignant melanoma (MM) make urgent demands on efficient response evaluation. In our previous researches, 18F-5-fluoro-N-(2-(diethylamino)ethyl)picolinamide (18F-5-FPN) exhibited high sensitivity, specificity and affinity to melanin. Photothermal therapy (PTT) exploits melanin to absorb and convert light energy into heat, which could kill tumor cells. The aim of this study was to further explore the feasibility of 18F-5-FPN PET to evaluate PTT therapy for MM, and comparing with that of 18F-FDG. Materials and Methods: Nude mice bearing B16F10 (melanoma cell) or MDA-MB-231 (breast cancer cell) were irradiated with an 808 nm laser for PTT. Survival analysis with Kaplan-Meier plots and Log-rank test was exploited to observe the therapy efficacy of PTT. 18F-5-FPN and 18F-FDG PET imaging were performed before and after PTT for therapy response evaluation in mice bearing B16F10 until 17 days after treatment. Furthermore, three different models, B16F10, MDA-MB-231 bearing nude mice and inflammatory models were prepared, and performed 18F-FDG and 18F-5-FPN PET imaging to further assess the specificity of 18F-FDG and 18F-5-FPN. Results: Melanin in B16F10 tumors successfully transformed optical energy into heat, and apparently framework destruction of tumor tissue and extensive necrosis were discovered by HE staining after 24 h of PTT. PTT prolonged the median survival of B16F10 models compared with untreated B16F10 mice (34 d vs. 9.5 d, P<0.001). The mean tumor uptakes of 18F-5-FPN on Day 2 (7.52 ± 3.65 %ID/g) and Day 6 (0.22 ± 6.00 %ID/g) after PTT were much lower than that those of before treatment 18.33 ± 4.98 %ID/g (P < 0.01). However, no significance existed between the 18F-FDG uptakes on Day 1 after PTT and before treatment (6.18 ± 1.18 %ID/g vs. 6.54 ± 0.84 %ID/g, P > 0.05), and the tumor uptakes on Day 5 elevated to 8.69 ± 2.75 %ID/g. For the three different models, 18F-5-FPN only accumulated in B16F10 tumor with 20.36 ± 4.38 %ID/g, but not in the MDA-MB-231 tumor (2.72 ± 0.49 %ID/g) and inflammation (1.14 ± 0.30 %ID/g). However, high uptakes of 18F-FDG were seen in all three models. Conclusion: Compared with 18F-FDG, 18F-5-FPN PET imaging was capable of estimating PTT response in MM, successfully monitored the occult recurrence after therapy, and perfectly distinguished MM from inflammation and other carcinomas. This potential probe may provide a new approach for precise and effective response evaluation, timely management of therapeutic regimen and sensitive follow-up. References:

Clinical Efficacy of Radiosynoviorthesis (RSV) in Elbow Joint Systemic Arthritis
I. Iakovou, T. Kotrotsios, E. Giannoula, A. Kalaitzoglou, C. Sachpekidis, G. Arsos;
Academic Dpt Of Nuclear Medicine, Papageorgiou Hsp, Thessaloniki, GREECE.

Aim/Introduction: To retrospectively evaluate the long term efficacy of radiosynoviorthesis (RSV) in patients with systemic (rheumatoid or psoriatic) arthritis of the elbow joint. Materials and Methods: 29 painful despite pharmacotherapy elbow joints of 28 patients (22 females, 67+-3 years old enrolled the study. They were intra-articularly injected with 2mci of 169Er citrate under x-ray guidance. In the pretherapeutic bone scan, all joints presented an positive blood pool image, indicative for active local synovitis. Joint functional status and pain were assessed by a visual analog scale (VAS) of ten steps: 1 - lack of any impairment to 10 - total disability just before (less than a week), a month and a year after treatment. Results: Twenty five in 28 patients (26 in 29 joints -90%) responded to therapy reporting a pronounced improvement in their manual activities as documented by the decrease of the mean VAS score prior to treatment from 8,3+-1,6 to 2,8+-1,9 (p<0,05) 12 months after RSV. Conclusion: RSV is a highly effective procedure in elbow’s systemic arthritis active synovitis. References: [Radiosynovectomy for the treatment of rheumatoid arthritis of the elbow joint]. Rozeboom S, Dörr U, Bihl H. Nuklearmedizin. 2001 Jun;40(3):91-7.

FDG PET/CT for early prediction of response to neoadjuvant therapy in HER2+ breast cancer: validation in a multicentric population
S. Tisserand1, S. Kanoun1, J. Blanc1, B. Coudert1, A. Berriolo-Riedinger1, F. Cachin2, L. Champion3, O. Humbert4, P. Salaun5, T. Mognetti6, K. Kerrou7;
1Centre Georges François Leclerc, Dijon, FRANCE, 2Centre Jean-Perrin, Clermont-Ferrand, FRANCE, 3Institut Curie, Paris, FRANCE, 4Centre Antoine Lacassagne, Nice, FRANCE, 5CHU Morvan, Brest, FRANCE, 6Centre Léon Bérard, Lyon, FRANCE, 7Hopital Tenon, Paris, FRANCE.

Aim/Introduction: Neoadjuvant therapy (NAC) including trastuzumab is a standard treatment in locally advanced breast cancer (BC) overexpressing HER2. Achieving pathologic complete response (pCR) at surgery is linked with better clinical outcome. Previous monocentric studies have shown the utility of FDG-PET/CT for early prediction of response in this setting, thanks to a high negative predictive value to identify nonresponders. However, multicentric validation is lacking and there are contradictory results regarding the best predictor of pCR, (early metabolic changes, or low residual metabolism after 1 or 2 cycles of therapy). The aim of this study was to determine in a multicentric population, the best metabolic parameters derived from FDG-PET/CT for early prediction of pCR after one cycle of NAC in HER2+ BC Materials and Methods: Patients were initially recruited in the AVATAXHER trial (EUDRACT 2009-013410-26), a prospective phase II multicentric study (26 participating centres) designed to investigate whether the addition of bevacizumab could improve the proportion of patients achieving pCR in patients unlikely to respond to treatment, based on FDG-PET/CT. For this ancillary study, only patients receiving conventional NAC (6 cycles of docetaxel+trastuzumab) were included. Each patient had FDG PET/CT before the first and second cycle of therapy in order to evaluate baseline and residual tumour metabolism (SUVmax, SUVpeak, SUVmean, MTV, TLG). The tumour metabolic response (ΔSUVmax, ΔSUVpeak, ΔSUVmean, ΔMTV, ΔTLG) was also calculated Results: Sixty-one patients were included. Of them, 34 (56%) reached pCR. There was no significant association between baseline tumour metabolism and pCR. In univariate analysis, low residual metabolism was significantly associated with pCR when considering SUVmax (p = 0.01, AUC=0.66), SUVmean (p = 0.006, AUC=0.66) and SUVpeak (p = 0.003, AUC=0.69). Tumour metabolic response was also correlated with pCR when considering ΔSUVmax (p = 0.001, AUC=0.71), ΔSUVpeak (p = 0.0009, AUC 0.72), and ΔSUVmean (p=0.002, AUC=0.71). Volume-based parameters, either baseline, residual or early changes, did not correlate with pCR. In multivariate analysis, ΔSUVmax remained an independent predictive factor of pCR (OR=8.87, p = 0.002) with high SBR grade Conclusion: Our results confirm the utility of FDG-PET/CT for early prediction of pCR after NAC in HER2+ BC. Among the various metabolic parameters tested, ΔSUVmax appears to be the most robust and appropriate in this multicentric population References: none

Pathologic neck node metastasis in Patients With Gynecologic Malignancy with neck node uptake on the F-18 FDG PET/CT
S. Yoon;
Department of Nuclear Medicine, Health Promotion Center, H plus New Yang-Ji Hospital, Department of Nuclear Medicine, Cheil General Hospital, Seoul, KOREA, REPUBLIC OF.

Aim/Introduction: Metastatic neck nodes limited to the lower neck including supraclavicular node are usually associated with primary malignancies below the clavicle. Prognosis of neck node metastasis of gynecologic malignancy is considered significant due to possibilities of combined further distant metastasis. We evaluated the pathologic type of primary malignant lesion and frequency of pathologic proven node metastasis in the patients with neck lymph nodal uptake on the F-18 fluorodeoxyglucose (FDG) PET-CT in the gynecologic cancer patients. Materials and Methods: Between April 2009 and December 2018, retrospectively 1600 patients with pathological-proven gynecologic malignancies including cervix cancer, endometrial cancer and ovarian cancer were evaluated. Thirty patients were suspected of neck lymph node metastasis in PET/CT and underwent a sono-guided neck lymph node biopsies. We evaluated the primary pathologic malignant lesion and histologic type of node metastasis in the patients with node metastasis in the neck. We evaluated the primary pathologic malignant lesion and the tumor marker in the patients with only single node metastasis in the neck. Results: Metastastic neck node on the PET-/CT in the patient with gynecologic malignancy was suspected in 30/1600 patients. 11 patients among 30 proven by sono guided aspiration biopsy of the neck nodes had node metastasis, other 19 patients showed benign reactive nodes. Among 11 patients with pathologically proven neck node metastasis, 7 among 17 cervical malignant lesion (41%) and 3 among 7 endometrial malignant lesion (43%) showed pathologic proven metastatic nodes. Histologic cell types showed 3 metastatic adenocarcinoma, 6 metastatic squamous cell carcinoma, 1 metastatic adenosquamous cell carcinoma and 1 lymphoma. Six patients (55%) among 11 patients with pathological proven neck node metastasis had pathologically only single neck node metastasis without any evidence of other metastatic nodes/lesions. Four cervix carcinoma with single neck node metastasis had normal tumor marker. One ovarian carcinoma also had normal tumor marker level. Only another one endometrial carcinoma showed elevated CA-125 Conclusion: Cervical carcinoma was the most common type of gynecologic malignancy with neck node metastasis. Six among 11 patients with neck node metastasis showed only single node metastasis without any metastasis outside the neck. And five patients with only single neck node metastasis had normal tumor marker level. Cervical carcinoma was the most common type of gynecologic malignancy with single node metastasis and normal tumor marker. We should attend suspicious neck node uptake on PET-CT albeit only single node uptake and normal tumor marker. References:

Bone marrow FDG uptake and correlation with bone marrow plasma cell infiltration rate and plasma cell morphology in Multiple Myeloma patients
A. Paschali1, E. Panagiotidis1, P. Mitsakis1, N. Papadopoulos1, T. Triantafyllou2, E. Giannoula1, M. Kotzasarlidou1, E. Verrou2, P. Konstantinidou2, V. Chatzipavlidou1, E. Katodritou2;
1Department of Nuclear Medicine, Theageneio Cancer Hospital, Thessaloniki, GREECE, 2Department of Hematology, Theageneio Cancer Hospital, Thessaloniki, GREECE.

Aim/Introduction: Multiple Myeloma (MM) is characterized by markedly heterogeneous phenotypic, genetic and clinical presentation. Aim of our study was to investigate possible correlations between bone marrow (BM) diffuse FDG uptake, plasma cell infiltration rate and plasma cell morphology. Materials and Methods: Thirty-three patients with MM either at diagnosis (n=11) or at relapse (n=22) were eveluated (M/F: 19/14, median age 62.5, range: 38-80, IgG: 19, IgA: 6, light-chain: 7, IgD: 1, ISS1: 12, ISS2: 14, ISS3: 7). Ηigh risk cytogenetics detected by FISH, including t(4;14), del17p and 1q+ were observed in 5 patients and t(11;14) was detected in 2 patients. Whole body 18F-FDG PET/CT studies were evaluated visually and semi quantitatively with the following parameters included in the analysis: BM metabolic state, number (Fn) and SUVmax of focal PET lesions, osteolysis number (Ln), presence and site of extramedullary disease (EM), paramedullary lesions (PM) and fractures(Fr), according to the IMPeTUs criteria (Nanni et al, EJNM 2018). For each patient we calculated the SUVmax ratio pelvis/liver using a circular region of interest (ROI) in the central portion of the liver far away from its edge, and a ROI within the pelvis (to include iliac crests and sacrum/L5) taking care not to include focal areas or other abnormality. Bone marrow aspirates of the iliac crest were performed within 4 weeks around the PET/CT examination. According to the plasma cell morphology we separated patients in groups of good, moderate and poor differentiation.
Results: The rate of clonal plasma cells (PCs) in the BM at the time of PET evaluation was ≥20% in 27/33 patients (PCs of good differentiation: 18/33, PCs of moderate/poor differentiation:15/33). In these 27 patients the patterns of skeletal FDG uptake were: diffuse (n=8), diffuse+focal (n=10), focal (n=6) and negative (n=3). Moderate or poor differentiation morphology and BM plasma cell infiltration rate≥20% both positively correlated with increased SUVmax pelvis/liver (p=0.05 and 0.02, respectively). Limb’s marrow involvement (femurs and humerals) was observed in all patients with diffuse axial marrow involvement, being more evident in those of moderate/poor differentiation. PM or EM disease significantly correlated with PCs’ morphology (p<0.05). Plasma cell morphology or rate of BM infiltration did not correlate with PET skeletal pattern, focal sites on PET or lytic lesions on CT. Conclusion: These preliminary data suggest that the sensitivity of PET in the detection of diffuse BM infiltration is dependant on plasma cell morphology and increases with the degree of undifferentiation. References: none

68Ga-PSMA PET/CT whole-body tumor burden in patients with biochemical recurrence of prostate cancer
A. Biggi Mattiolli, M. C. L. Lima, M. Camacho, C. D. Ramos, A. O. Santos, E. Etchebehere;
Medicina Nuclear de Campinas, Campinas, BRAZIL.

Aim/Introduction: In solid tumors, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in 18F-FDG PET/CT studies showed to correlate with prognosis. In prostate cancer patients submitted to Ra-223 therapy, fluoride tumor volume and total fluoride uptake on lesions in 18F-Fluoride PET/CT have shown to correlate with prognosis1. However, the determination of PSMA-68Ga tumor burden of PSMA in lesions (whole-body PSMA tumor volume-PSMA-TV and the whole-body total uptake-PSMA-TL) in 68Ga-PSMA PET/CT has not been extensively studied2. The objective of this project is to evaluate whether the serum PSA values and clinical parameters are associated with PSMA-TV and PSMA-TL. Materials and Methods: We retrospectively evaluated 211 patients with prostate cancer submitted to 68Ga-PSMA PET/CT due to biochemical recurrence. In 68Ga-PSMA PET/CT positive studies, the tumor burden parameters PSMA-TV and PSMA-TLG were calculated with a semi-automatic software (MFS tool; Syngo.Via VB20; Siemens Medical Solutions, Chicago, IL). The images were then reviewed to exclude any areas of physiologic uptake and to include pathologic areas with relatively low uptake. PSMA tumor burden metrics were correlated to clinical the following parameters age, free PSA levels (PSAf), total PSA levels (PSAt), Gleason score and the highest SUVmax lesion. Results: Among the 140 patients that underwent 68Ga-PSMA PET/CT studies, 114 were positive and thus used to calculate the PMSA-TV and PSMA-TL tumor burden parameters. The mean PMSA-TV was 28.54 cm3 and PMSA-TL was 207.99. There was a direct correlation between age and the PMSA-TV (p = 0.0056) and PSMA-TL (p = 0.0004) values. Higher PSAf and PSAt levels were associated with higher tumor burden values of PMSA-TV (p = 0.0002 and p <0.0001, respectively) and of PSMA-TLV (p <0.0001 and p <0.001, respectively). The ​​SUVmax values only showed a direct and positive correlation with PSMA-TL (p <0.0001). Conclusion: In biochemical recurrence of prostate cancer, the whole-body tumor burden on 68Ga-PSMA PET/CT has a direct and positive correlation with serum PSA values and age. Further work is needed to establish if PSMA-TL and PSMA-TV is a strong and independent prognostic imaging biomarker able to determine therapy response. References: 1. Etchebehere EC et. al. Prognostic factors in patients treated with 223Ra: the role of skeletal tumor burden on baseline 18F-fluoride PET/CT in predicting overall survival. J Nucl Med 2015. 2. Schmidkonz C et. al. 68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer. Eur J Nucl Med Mol Imaging 2018.

Retrospective cohort study to assess the prognostic value of baseline necrosis on PET-CT imaging in Hodgkin lymphoma
I. Chen, N. Borges, L. Winn, W. Osborne, G. Petrides;
Freeman Hospital, Newcastle Upon Tyne, UNITED KINGDOM.

Aim/Introduction:   Identifying prognostic markers at diagnosis is essential to determine optimal tailored therapy for patients. The presence of necrosis has been shown to be associated with inferior outcomes in patients with diffuse large B cell lymphoma (1). This retrospective cohort study assesses whether necrosis at baseline correlates with clinical outcomes in patients with Hodgkin lymphoma. Materials and Methods:   All available baseline PET-CT scans of patients diagnosed with Hodgkin lymphoma between January 2015 and December 2016 at a large UK teaching hospital were reviewed for evidence of tumour necrosis by a consultant radionuclide radiologist with a specialist interest in lymphoma. Potential necrosis identified on PET-CT was then confirmed visually and quantitatively on alternative imaging. The presence or absence of necrosis was correlated with prognostic markers (Total Metabolic Volume (TMV), Total Lesion Glycolysis (TLG) International Prognostic Index (IPI) (Hasenclever Index)) and response assessment (metabolic response, current remission status, relapse outcome and mortality). Results: Fifty three patients’ PET-CT scans were reviewed in total. Ten patients were confirmed to have necrosis on both PET-CT and alternative imaging. The presence of necrosis was associated with increased total mortality (40%) vs no necrosis (16%); Kaplan Meier survival analysis demonstrated a significant difference between the necrosis cohort compared with the no necrosis cohort using the log rank test (p = 0.042). The presence of necrosis did not correlate with other prognostic markers (TMV, TLG or IPI). Conclusion: The presence of necrosis on baseline PET-CT scan in patients receiving frontline treatment for Hodgkin lymphoma significantly correlates with increased patient mortality. Tumour necrosis did not significantly correlate with other prognostic markers. Identifying high risk patients at diagnosis is important. The current UK practice of delivering more intensive frontline therapy to patients with a high IPI is suboptimal and intensifying treatment after a positive interim PET scan is also associated with poor outcomes. Robust prognostic markers at diagnosis are a priority for the management of patients with Hodgkin Lymphoma. This study has identified a new independent prognostic marker in Hodgkin Lymphoma and prospective clinical trials are required. References: 1. Adams HJA, de Klerk JMH, Fijnheer R, Dubois SV, Nievelstein RAJ, Kwee TC. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma. Eur J Radiol. 2015 Mar;84(3):372-377.

Metabolic Tumor Volume Predicts Short-Term Progression After Immunotherapy in Non Small Cell Lung Cancer
D. Chardin, M. Paquet, J. Darcourt, J. Otto, O. Humbert;
Centre Antoine Lacassagne, Nice, FRANCE.

Aim/Introduction: Baseline markers are needed to predict outcome after immunotherapy. This study aimed to investigate the predictive value of total metabolic tumor volume (MTV) measured from baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. Materials and Methods: From February 2017 to September 2018, 54 patients scheduled to initiate immunotherapy (pembrolizumab or nivolumab) as their first or later systemic treatment for metastatic NSCLC were prospectively evaluated in this non-randomized, current-care study in our institution. FDG PET was performed at baseline. Standardized uptake values of lesion with the highest uptake (SUVmax) was measured. Total MTV was obtained using à threshold based on 41% of the SUVmax in each lesion. Short-term progression was defined as progression and treatment stop within 3 months after the beginning of immunotherapy. Deaths within a 6 month follow up period were recorded. Univariate analyses and ROC analyses were performed to identify predictors of short-term progression. Results: Mean patient’s age was 63±10 years. The pathological subtype was squamous cell carcinoma and adenocarcinoma in 80% and 20% of patients, respectively. On PET, median SUVmax was calculated at 14.2 [range: 6.3-64.0] and median MTV was measured at 31mL [range:2mL-308mL]. Sixteen patients presented with short-term progression after immunotherapy. By univariate analyses, a higher MTV was significantly associated with short-term progression (cut-off=31mL, HR=7.14; 95% CI: 1.6-45.9; p=0.006). A short-term progression was observed in 46% of patients with MTV >31 mL vs 11% of patients with MTV < 31mL. SUVmax did not show any correlation with short-term progression (p>0.05). ROC curve analysis of MTV to predict short-term progression revealed an AUC of 0.81 (95% CI: 0.69-0.92). Concerning overall survival, 7/27 patients with an MTV > 31 mL died during the 6 months follow-up, whereas 3/27 deaths were observed in patients with MTV < 31mL. Conclusion: MTV has a potential value in predicting short-term progression after immunotherapy in patients with NSCLC. Indeed, a high MTV is associated with a higher risk of short-term progression and could predict death within 6 months. References: none

[68Ga]Ga-PSMA-11 PET/CT For Monitoring Response to Treatment in Metastatic Prostate Cancer - is there an Added Value over Standard Follow-up?
J. Kuten, D. Sarid, O. Yossepowitch, N. J. Mabjeesh, E. Even-Sapir;
Tel Aviv Sourasky Medical Center, Tel Aviv, ISRAEL.

Aim/Introduction: The aim of the current study was to assess whether, and to what extent, follow-up PSMA-based PET/CT studies add value to the routine clinical follow-up during treatment of patients with metastatic prostate cancer (PCa).
Materials and Methods: The study cohort was composed of 52 patients with metastatic PCa who underwent [68Ga]Ga-PSMA-11 PET/CT imaging and PSA level measurements before and during treatment. Response was categorized as improvement, stable disease and disease progression by serum PSA dynamics and compared to change in imaging findings on pre- and post-treatment PET/CT. McNemar’s test was used to assess agreement between PET/CT- and PSA-based response to treatment.
Results: Most patients (65.4%) had compatible biochemical- and imaging- based response to treatment. However, in 18/52 patients (34.6%) imaging and biochemical response, were discrepant. In 5/52 patients (9.6%) PET/CT “upstaged” and in 13/52 (25%) it “downstaged" disease compared to biochemical assessment. Discrepancy between imaging and biochemical response was most prominent in biochemically-stable patients (90.9%), followed by patients with biochemical-progression (33.3%) and only in 8.7% of patients with biochemical improvement. In 22 of 30 patients (73.3%) with longer follow-up, imaging response was relevant for treatment choice. Relevance of imaging response was reflected by its ability to assess individual lesions in case of heterogeneous lesion response, appearance of new lesions, and identification of lesions requiring specific attention such as targeting radiotherapy. Conclusion: Results of this retrospective analysis show that biochemical response to treatment and [68Ga]Ga-PSMA-11 PET/CT-based response assessment differ in a third of metastatic PCa patients, often in view of the ability of imaging to allow for lesion-based and not only patient-based analysis. Monitoring response during treatment by [68Ga]Ga-PSMA-11 PET/CT is relevant for decision-making and choosing treatment in the majority of patients. References: none.

Artificial intelligence can discriminate between focal and normal bone/bone marrow uptake in lymphoma patients staged with FDG-PET/CT- a descriptive study
M. Sadik1, A. Krupic1, A. Dudás1, J. Lopez Urdaneta1, J. Ulén2, O. Enqvist3,2, P. Andersson4, L. Edenbrandt1;
1Nuclear Medicine, Gothenburg, SWEDEN, 2Eigenvision AB, Malmö, SWEDEN, 3Chalmers University of Technology, Gothenburg, SWEDEN, 4Hematology, Gothenburg, SWEDEN.

Aim/Introduction: Localized bone marrow involvement on FDG-PET/CT in newly diagnosed lymphoma patients has prognostic implications. A growing body of evidence suggest that FDG-PET/CT can replace bone marrow biopsy in some patients, avoiding unnecessary procedures and pain. As a first step we aim to study whether artificial intelligence (AI) can discriminate between localized and normal bone/bone marrow uptake. Materials and Methods: All newly diagnosed Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) patients who had undergone a staging PET/CT between 2011-2016 at Sahlgrenska University hospital were retrospectively included. Information regarding bone and bone marrow involvement were extracted from the final clinical assessment done by hematologists. In a previous work AI was trained to find the skeletal anatomy (1). Bone less than 7 mm from the bone surface were removed to isolate the bone marrow. A threshold was defined as the average SUV + 2 SD for the vertebral bone marrow. Any bone marrow voxels with SUV above this threshold were classified as lesion and the total lesion uptake (TLU) was calculated as (average lesion SUV - threshold) x (total lesion volume in mL). A TLU > 0,8 was considered pathological. Results: The total cohort consisted of 151 patients, of whom 72 (48%) patients were female. Median age was 34 years (10-85 years). Most patients had HL (87%) and the rest DLBCL. Eighteen patients were classified as having focal uptake by AI. Of those, 14 patients (78%) were classified as true positive and 4 (22%) as false positive. 133 patients were classified as normal by AI resulting in 127 (95%) patients classified as true negative and six (5%) as false negative. Conclusion: Our results show that AI can differentiate between normal and pathological bone/bone marrow uptake. This method can highlight pathological regions to focus the physician’s attention and in the future standardize the PET/CT image reading. References: (1) Lindgren Belal S, Sadik M, Kaboteh R, Enqvist O, Ulén J, Poulsen MH, Simonsen J, Høilund-Carlsen PF, Edenbrandt L, Trägårdh E. Deep learning for segmentation of 49 selected bones in CT scans: First step in automated PET/CT-based 3D quantification of skeletal metastases. Eur J Radiol. 2019 Apr;113:89-95.

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