Semi-automatic tumor delineation for evaluation of 64Cu-DOTATATE PET/CT in patients with neuroendocrine neoplasms: prognostication based on lowest lesion uptake and total tumor volume

SummaryAim: In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in 177Lu-PSMA-617 therapy was evaluated.Methods: Eleven consecutive prostate cancer patients receiving a first cylcle of 177Lu-PSMA-617 (administered activity of approximately 6GBq) were included. The 68Ga-PSMA-11 PET/CT scan previous to therapy was used to determine TTV and SG uptake (glandulae submandibularis) employing PMOD version 3.403 with different 68Ga-PSMA-11 thresholds based on the standardized uptake value (SUV).The kidney dose was estimated with the software ULMDOS using planar whole-body scintigrams.Results: Kidney dose and SG uptake was inversely correlated to TTV, indicating high kidney dose and high SG uptake in case of low tumor load and low kidney dose and low SG uptake in case of high tumor load.Conclusion: Our data support the hypothesis that in 177Lu-PSMA-617 therapy an individualized treatment activity based on total tumor volume could be beneficiary.

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PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05040-1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Robert Seifert ◽

Katharina Kessel ◽

Katrin Schlack ◽

Manuel Weber ◽

Ken Herrmann ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Tumor Volume ◽

Cox Regression ◽

Radioligand Therapy ◽

Total Tumor Volume ◽

Psma Pet ◽

Pet Ct ◽

Lesion Number ◽

Patients At Risk

Abstract Introduction [177Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy. Methods A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUVmean), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUVmean) were quantified for each patient. Log2 transformation was used for regressions. Results Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value. Conclusion PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.

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Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.07.000774 ◽

2020 ◽

Vol 92 (7) ◽

pp. 55-62

Author(s):

E. S. Nesterova ◽

G. A. Yatsyk ◽

N. S. Lutsik ◽

S. K. Kravchenko ◽

A. B. Sudarikov ◽

...

Keyword(s):

Tumor Tissue ◽

Tumor Volume ◽

Whole Body ◽

Resonance Imaging ◽

Total Tumor Volume ◽

Positron Emission ◽

Tumor Lesion ◽

Pet Ct ◽

Weighted Magnetic Resonance Imaging ◽

And Diffusion

Aim.This study conducted the possibilities of diffusion-weighted magnetic resonance imaging of the whole body diffusion WB-MRI (in comparison with positron emission tomography with computed tomography PET/CT) in assessing the volume and prevalence of the tumor, as well as determining bone marrow (BM) damage (for various cytological types) in the diagnosis and staging of the disease in patients with FL. Materials and methods.A prospective comparative search study included 15 patients (4 men and 11 women, with a median age of 53 years) with newly diagnosed FL. Patients have not received antitumor chemotherapy previously. After the diagnosis was established, all patients (with the blindness of both the cases themselves and some specialists regarding the results of other specialists) were examined by PET/CT and diffusion WB-MRI, after which a BM examination was performed (histological examination and determination of B-cell clonality in BM puncture by PCR). Using the diffusion WB-MRI method, the prevalence of tumor lesion (nodal and extranodal foci) in each patient was estimated, and the total tumor volume was calculated, BM lesion was detected, and BM lesion volume was calculated. For lesions of different localization, the measured diffusion coefficient (DC) of the diffusion WB-MRI and the standardized rate of accumulation of the radiopharmaceutical in tissues (SUV) of the PET/CT method were determined and compared with each other (for the same areas). Statistical analysis was performed using the estimate of agreement (by Cohens kappa coefficient and asymptotic test) of the results of the compared methods. Results.Estimates of the prevalence of tumor damage (lymph nodes and extranodal foci) using the diffusion WB-MRI and PET/CT methods were the same. High DC and SUV were observed in the peripheral lymph nodes, extranodal foci and bulky, low DC and SUV in the foci of BM. All 4 methods successfully determined BM damage, however, the diffusion WB-MRI had comparatively less negative results. The highest values of SUV and CD were noted in cases of the 3 grade of FL. Using the diffusion WB-MRI method, the prevalence of tumor lesion was assessed in each patient (nodal and extranodal foci were detected) and the total tumor volume was calculated, BM lesion detection was performed, and the volume of BM lesion was calculated. It is important to note that with the help of diffusion WB-MRI, it was possible to measure separately the total tumor volume (462025 cm3) and separately the volume of bulky (251358 cm3). The diffusion WB-MRI allowed us to differentiate the volume of tumor tissue (reduced as a result of treatment) and residual (fibrous-adipose) tissue in residual formations (which averaged 21% of the initial volume). The predictors of a poor antitumor response were the maximum SUV values (more than 14.0) and the minimum DC values (0.510-3mm2/s) in the BM foci. Conclusion.The diffusion WB-MRI allows for detailed visualization of BM lesions and surrounding soft tissues both in the debut of the FL and in the process of tracking the effectiveness of chemotherapy, which makes it possible to use it along with PET/CT. Diffusion WB-MRI allows to separately evaluate the volume of true tumor tissue and residual tissue. Cases of the 3 grade of FL (including the transformation of FL into diffuse B-large cell lymphoma) are isolated due to low DC values (and high SUV values) in the tumor tissue. BM foci of FL lesion also have (in comparison with nodal and extranodal foci) lower DC values. The predictors of a poor antitumor response were high (from 14.0 or more) SUV valuesin the tumor (and especially in bulky), and low (about 0.5103mm2/s) DC values of BM foci. The PET/CT and diffusion WB-MRI have proven to be reliable diagnostic tools for establishing the stage of FL and detecting BM damage. Diffusion WB-MRI for FL is an informative first-line diagnostic method that allows regular monitoring of the disease and early detection of foci of relapse and disease progression.

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Feasibility of Different Tumor Delineation Approaches for 18F-PSMA-1007 PET/CT Imaging in Prostate Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.663631 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lena M. Mittlmeier ◽

Matthias Brendel ◽

Leonie Beyer ◽

Nathalie L. Albert ◽

Andrei Todica ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Metastatic Prostate Cancer ◽

Tumor Volume ◽

Reference Standard ◽

Tumor Delineation ◽

Contrast Enhanced Ct ◽

Volume Delineation ◽

Psma Pet ◽

Pet Ct

BackgroundDelineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68Ga-labeled ligands; nonetheless, 18F-labeled PET ligands are gaining increasing importance due to advantages over 68Ga-labeled compounds. However, standardized tumor delineation methods for 18F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18F-PSMA-1007 PET.MethodsFifty patients with metastatic prostate cancer, 18F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to III) liver (SUVliver), IV) parotis (SUVparotis) and V) spleen (SUVspleen).ResultsA fixed SUV of 4.0 (r=0.807, r2 = 0.651, p<0.001) showed the best overall association with the volumetric reference. 55% SUVmax (r=0.627, r2 = 0.393, p<0.001) showed highest association using an isocontour-based threshold. Best background-based approaches were 60% SUVliver (r=0.715, r2 = 0.511, p<0.001), 80% SUVparotis (r=0.762, r2 = 0.581, p<0.001) and 60% SUVspleen (r=0.645, r2 = 0.416, p<0.001). Background tissues SUVliver, SUVparotis & SUVspleen did not correlate (p>0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUVmax, 42% SUVmax and 20% SUVmax) revealed inferior association for LNM delineation.ConclusionsA threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated.

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Comparison of pretherapeutic osseous tumor volume and standard hematology for prediction of hematotoxicity after PSMA-targeted radioligand therapy

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05412-1 ◽

2021 ◽

Author(s):

Liam Widjaja ◽

Rudolf A. Werner ◽

Tobias L. Ross ◽

Frank M. Bengel ◽

Thorsten Derlin

Keyword(s):

Multivariate Analysis ◽

Tumor Volume ◽

Predictive Performance ◽

Castration Resistant Prostate Cancer ◽

Operating Characteristics ◽

Predictive Capability ◽

Radioligand Therapy ◽

Castration Resistant ◽

Pet Ct ◽

Late Stages

Abstract Purpose Hematotoxicity is a potentially dose-limiting adverse event in patients with metastasized castration-resistant prostate cancer (mCRPC) undergoing prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT). We aimed to identify clinical or PSMA-targeted imaging-derived parameters to predict hematological adverse events at early and late stages in the treatment course. Methods In 67 patients with mCRPC scheduled for 177Lu-PSMA-617 RLT, pretherapeutic osseous tumor volume (TV) from 68Ga-PSMA-11 PET/CT and laboratory values were assessed. We then tested the predictive capability of these parameters for early and late hematotoxicity (according to CTCAE vers. 5.0) after one cycle of RLT and in a subgroup of 32/67 (47.8%) patients after four cycles of RLT. Results After one cycle, 10/67 (14.9%) patients developed leukocytopenia (lymphocytopenia, 39/67 [58.2%]; thrombocytopenia, 17/67 [25.4%]). A cut-off of 5.6 × 103/mm3 for baseline leukocytes was defined by receiver operating characteristics (ROC) and separated between patients with and without leukocytopenia (P < 0.001). Baseline leukocyte count emerged as a stronger predictive factor in multivariate analysis (hazard ratio [HR], 33.94, P = 0.001) relative to osseous TV (HR, 14.24, P = 0.01). After four cycles, 4/32 (12.5%) developed leukocytopenia and the pretherapeutic leukocyte cut-off (HR, 9.97, P = 0.082) tended to predict leukocytopenia better than TV (HR, 8.37, P = 0.109). In addition, a cut-off of 1.33 × 103/mm3 for baseline lymphocytes separated between patients with and without lymphocytopenia (P < 0.001), which was corroborated in multivariate analysis (HR, 21.39, P < 0.001 vs. TV, HR, 4.57, P = 0.03). After four cycles, 19/32 (59.4%) developed lymphocytopenia and the pretherapeutic cut-off for lymphocytes (HR, 46.76, P = 0.007) also demonstrated superior predictive performance for late lymphocytopenia (TV, HR, 5.15, P = 0.167). Moreover, a cut-off of 206 × 103/mm3 for baseline platelets separated between patients with and without thrombocytopenia (P < 0.001) and also demonstrated superior predictive capability in multivariate analysis (HR, 115.02, P < 0.001 vs.TV, HR, 12.75, P = 0.025). After four cycles, 9/32 (28.1%) developed thrombocytopenia and the pretherapeutic cut-off for platelets (HR, 5.44, P = 0.048) was also superior for the occurrence of late thrombocytopenia (TV, HR, 1.44, P = 0.7). Conclusions Pretherapeutic leukocyte, lymphocyte, and platelet levels themselves are strong predictors for early and late hematotoxicity under PSMA-directed RLT, and are better suited than PET-based osseous TV for this purpose.

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Tumor volume-adapted SUVN as an alternative to SUVpeak for quantification of small lesions in PET/CT imaging: a proof-of-concept study

Japanese Journal of Radiology ◽

10.1007/s11604-021-01112-w ◽

2021 ◽

Author(s):

Mohammad Amin Mosleh-Shirazi ◽

Zahra Nasiri-Feshani ◽

Pardis Ghafarian ◽

Mehrosadat Alavi ◽

Gholamhasan Haddadi ◽

...

Keyword(s):

Tumor Volume ◽

Ct Imaging ◽

Proof Of Concept ◽

Concept Study ◽

Pet Ct

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Interim 4′-[methyl-11C]-thiothymidine PET for predicting the chemoradiotherapeutic response in head and neck squamous cell carcinoma: comparison with [18F]FDG PET

EJNMMI Research ◽

10.1186/s13550-021-00749-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Katsuya Mitamura ◽

Takashi Norikane ◽

Yuka Yamamoto ◽

Kengo Fujimoto ◽

Yasukage Takami ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Fdg Pet ◽

Tumor Volume ◽

Standardized Uptake Value ◽

Complete Response ◽

Neck Squamous Cell Carcinoma ◽

Pet Ct

Abstract Purpose We investigated the potential of interim 4′-[methyl-11C]thiothymidine ([11C]4DST) PET for predicting the chemoradiotherapeutic response for head and neck squamous cell carcinoma (HNSCC), in comparison with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET. Methods A total of 32 patients with HNSCC who underwent both [11C]4DST and [18F]FDG PET/CT before therapy (baseline) and at approximately 40 Gy point during chemoradiotherapy (interim) were available for a retrospective analysis of prospectively collected data. The baseline was treatment-naïve PET/CT scan as part of staging. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) from [18F]FDG PET or proliferative tumor volume (PTV) from [11C]4DST PET, and total lesion glycolysis (TLG) from [18F]FDG PET or total lesion proliferation (TLP) from [11C]4DST PET were measured. MTV or PTV was defined as the volume with an SUVmax greater than 2.5. The differences in SUVmax (ΔSUVmax), MTV (ΔMTV) or PTV (ΔPTV) and TLG (ΔTLG) or TLP (ΔTLP) from baseline to interim PET scans were calculated. Patients without or with evidence of residual or recurrent disease at 3 months after completion of chemoradiotherapy were classified as showing a complete response (CR) and non-CR, respectively. Results All patients showed increased uptake in primary tumor on baseline [11C]4DST and [18F]FDG PET studies. All patients showed increased uptake on interim [18F]FDG PET, whereas 18 patients showed no increased uptake on interim [11C]4DST PET. After chemoradiotherapy, 25 patients were found to be in CR group and 7 to be in non-CR group. [11C]4DST ΔSUVmax, ΔPTV, and ΔTLP for CR group showed significantly greater reductions than the corresponding values for non-CR group (P = 0.044, < 0.001, < 0.001, respectively). However, there were no significant differences in [18F]FDG ΔSUVmax, ΔMTV, or ΔTLG between CR group and non-CR group. [11C]4DST ΔMTV of -90 was the best cutoff value for the early identification of patients with non-CR. Conclusion These preliminary results suggest that interim [11C]4DST PET might be useful for predicting the chemoradiotherapeutic response in patients with HNSCC, in comparison with [18F]FDG PET.

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Total metabolic tumor volume and spleen metabolism on baseline [18F]-FDG PET/CT as independent prognostic biomarkers of recurrence in resected breast cancer

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05322-2 ◽

2021 ◽

Author(s):

Romain-David Seban ◽

Roman Rouzier ◽

Aurelien Latouche ◽

Nicolas Deleval ◽

Jean-Marc Guinebretiere ◽

...

Keyword(s):

Breast Cancer ◽

Fdg Pet ◽

Tumor Volume ◽

Metabolic Tumor Volume ◽

Prognostic Biomarkers ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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Impact of [18F]FDG-PET and [18F]FLT-PET-Parameters in Patients with Suspected Relapse of Irradiated Lung Cancer

Diagnostics ◽

10.3390/diagnostics11020279 ◽

2021 ◽

Vol 11 (2) ◽

pp. 279

Author(s):

Tine N. Christensen ◽

Seppo W. Langer ◽

Gitte Persson ◽

Klaus Richter Larsen ◽

Annemarie G. Amtoft ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Fdg Pet ◽

Tumor Volume ◽

High Dose ◽

Flt Pet ◽

Pet Ct ◽

Radiation Induced ◽

Fdg Pet Ct ◽

Induced Changes

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01–1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.

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