Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas that can develop either de novo or as a result of malignant transformation of neurofibromas. Diagnostic modalities of choice, such as MRI or 18F-FDG PET/CT, show high sensitivity for the detection of MPNSTs but moderate specificity, as MPNSTs and benign peripheral nerve sheath tumors (BPNSTs) can initially present similar clinical and radiologic pictures. PET/CT with 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) showed specific uptake in sarcomas and enabled differentiation of benign and malignant lesions in other entities. Here, we analyzed the ability of 68Ga-FAPI PET/CT to differentiate between MPNSTs and BPNSTs. Methods: Twenty-six patients with suspected or histologically confirmed peripheral nerve sheath tumors who were scheduled to have surgical resection/biopsy underwent 68Ga-FAPI-46 PET/CT with static and dynamic acquisition. SUVmax, SUVmean, maximum and mean tumor-to-background ratios, and time-activity curves were evaluated using volume-of-interest-based analysis (isocontour 50%). Time to peak was derived from time-activity curves. Statistical analyses were performed, and receiver-operating-characteristic curves were calculated. Exemplary target validation by fibroblast activation protein immunohistochemistry was performed in 13 cases. Results: Eighteen patients (4 with MPNSTs, 5 with neurofibromas, 9 with schwannomas) were included in the final analysis. MPNSTs showed significantly higher 68Ga-FAPI uptake compared with BPNSTs. Neurofibromas showed higher 68Ga-FAPI uptake compared with schwannomas. In dynamic imaging, time to peak of MPNSTs and neurofibromas was prolonged compared with schwannomas. Analysis of receiver-operating-characteristic curves displayed high sensitivity (100%) and specificity (92.86%) of 68Ga-FAPI PET/CT for discrimination of MPNSTs and BPNSTs, for an exploratory SUVmax cutoff value of 7.53. Fibroblast activation protein expression was strong in MPNSTs and moderate in BPNSTs. Conclusion: 68Ga-FAPI PET/CT may aid in differentiating between MPNSTs and BPNSTs, thereby improving lesion characterization in indeterminate MRI or 18F-FDG PET/CT scenarios.

Oncological treatment in a substantial portion of patients with cancer of unknown primary (CUP) remains challenging due to limitations of conventional imaging and positron emission tomography/computed tomography with 18Fluor-fluorodeoxyglucose (18F-FDG-PET/CT). In head and neck-like CUP (HNCUP), several studies found significantly higher tracer-uptake and detection rates of primary tumors in 68Gallium-labeled fibroblast activation protein inhibitor-PET/CT (68Ga-FAPI-PET/CT). Here, we address a gap in CUP literature by retrospectively evaluating the diagnostic accuracy of both tracer in a head-to-head comparison of patients with single-site and oligometastatic extra-cervical CUP. 13 patients with extra-cervical CUP underwent both 18F-FDG- and 68Ga-FAPI-PET/CT. Suspicious PET-positive lesions were delineated using the volume of interest-technique (50

Purpose:Whether FDG-PET-guided de-escalation of elective target volumes in radiotherapy of the head and neck reduces late toxicity remains uncertain. Therefore, we compared predicted toxicity of two de-escalation strategies-reduced elective nodal irradiation (RNI) and involved node irradiation (INI)-with standard elective nodal irradiation (ENI). Materials and Methods:In a within-patient plan comparison (n = 26), we generated RNI and INI plans using the same FDG-PET informed high-/intermediate-risk targets as ENI. RNI limited elective volumes to within 2 cm cranio-caudal from gross disease; INI omitted elective treatment. Proton plans were created in representative oropharyngeal cases. Co-primary outcomes were six-month normal-tissue complication probabilities (NTCPs) for dysphagia, feeding-tube dependence, and xerostomia. Results:Median total planning target volume decreased from 540 cm3 (ENI) to 418 cm3 (RNI) and 173 cm3 (INI). RNI and INI reduced modeled dysphagia risk by 5.9 percentage points (pp) (95% CI 2.3 to 9.6 pp; padj = 0.005) and 11.0 pp (6.9 to 15.2 pp; padj < 0.001), feeding-tube dependence by 2.8 pp (1.2 to 4.5 pp; padj = 0.005) and 4.2 pp (2.5 to 6.0 pp; padj < 0.001), and xerostomia by 2.8 pp (0.0 to 5.7 pp; padj = 0.054) and 8.8 pp (5.5 to 12.2 pp; padj < 0.001), respectively. Predicted benefits were greatest in hypopharyngeal and laryngeal cancers. In selected cases, de-escalated proton therapy further reduced organ-at-risk dose. Conclusions:FDG-PET-guided volumetric de-escalation was associated with lower modeled late swallowing-related toxicity. These findings support the rationale for ongoing and future trials investigating volumetric de-escalation strategies.

Ziel/Aim: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are a rare disease [1] [2]. Current guidelines recommend treatment with somatostatin receptor (SSTR) targeting radioligand therapy (RLT) [1] [3]. SSTR-RLT is available as 177Lu-radiolabeled somatostatin analogues locally compounded by hospitals (non-licensed product) and as EMA approved product with standardized formulation and application. Limited real-world data exist on the German care situation with SSTR-RLT.

Ziel/Aim: Mit der Zulassung von PLUVICTO (177Lu-PSMA-617-Therapie) stieg die Zahl der benötigen PSMA-PET/CTs durch die notwendige Evaluation der PSMA-Expression vor Therapie stetig an. Jedoch ist die Kapazität dieser Untersuchungsmethode begrenzt, sodass die PSMA-Szintigraphie mit 99mTc eine mögliche Alternative zur Evaluation der Therapiefähigkeit darstellt. Ziel ist Überprüfung der Eignung einer PSMA-Szintigraphie mit GCK-01-Ligand zur Patientenselektion vor PSMA-Ligandentherapie im direkten Vergleich mit dem Gold-Standard der PSMA-PET/CT im Rahmen der VISION-Studie.

Ziel/Aim: Beim Prostatakarzinom sind bildgebende Verfahren wie CT und MRT in ihrer Fähigkeit eingeschränkt, kleine Lymphknotenmetastasen zu erkennen. Eine genauere Darstellung von Metastasen ermöglicht die PSMA-PET/CT. Die aktuellen Zielvolumenempfehlungen basieren jedoch meist auf älteren Daten ohne Hybridbildgebung. Dies birgt das Risiko, dass Metastasen außerhalb des Zielvolumens übersehen werden und die Effektivität der Therapie reduziert wird. Diese Arbeit untersucht die Verteilung von Lymphknotenmetastasen bei Patienten mit Prostatakarzinom mittels PSMA-PET/CT und vergleicht diese mit aktuellen Zielvolumenempfehlungen.

The aim of this work is to evaluate our clinical real -world data obtained with 225 Ac-PSMA-617 (AcPSMA), which were acquired under compassionate care regulations in patients with advanced -stage prostate cancer. The objective parameters that could be derived from this evaluation are compared with previous literature about AcPSMA and 177 Lu-PSMA-617 (LuPSMA). Methods: The medical files of all patients who had received AcPSMA on an individual patient basis at the Heidelberg University Hospital since January 2014 were analyzed retrospectively. Previously published patients were excluded. The remaining patients were tailored into 2 subgroups with different treatment strategies: group 1 received AcPSMA as a deescalated monotherapy, and group 2 received LuPSMA plus AcPSMA as a cocktail regimen. Baseline characteristics, serum prostate -specific antigen (PSA) response, and overall survival were compared with the most appropriate historical controls. Results: Of 287 patients treated, 54 were excluded because of previous publication and 233 were evaluated, 104 of whom received AcPSMA monotherapy (median, 6 MBq). In this group, 55 patients (53%) presented with a best PSA response of at least 50%. The other 129 patients received a cocktail therapy of AcPSMA (median, 4 MBq) plus LuPSMA (4 GBq). In this group, a best PSA response of at least 50% was observed in 74 patients (57%). The median overall survival in the monogroup was 9 mo and in the cocktail group was 15 mo. If adjusted for prognostic baseline characteristics, the efficacy of both regimens was not significantly different. Conclusion: Deescalated treatment activities of AcPSMA or AcPSMA and LuPSMA cocktail regimens present better tolerability with regard to xerostomia than previous regimens of at least 100 kBq/kg while retaining high antitumor activity in poor -prognosis prostate cancer patients.

The aim of this work is to evaluate our clinical real-world data obtained with 225Ac-PSMA-617 (AcPSMA), which were acquired under compassionate care regulations in patients with advanced-stage prostate cancer. The objective parameters that could be derived from this evaluation are compared with previous literature about AcPSMA and 177Lu-PSMA-617 (LuPSMA). Methods: The medical files of all patients who had received AcPSMA on an individual patient basis at the Heidelberg University Hospital since January 2014 were analyzed retrospectively. Previously published patients were excluded. The remaining patients were tailored into 2 subgroups with different treatment strategies: group 1 received AcPSMA as a deescalated monotherapy, and group 2 received LuPSMA plus AcPSMA as a cocktail regimen. Baseline characteristics, serum prostate-specific antigen (PSA) response, and overall survival were compared with the most appropriate historical controls. Results: Of 287 patients treated, 54 were excluded because of previous publication and 233 were evaluated, 104 of whom received AcPSMA monotherapy (median, 6 MBq). In this group, 55 patients (53%) presented with a best PSA response of at least 50%. The other 129 patients received a cocktail therapy of AcPSMA (median, 4 MBq) plus LuPSMA (4 GBq). In this group, a best PSA response of at least 50% was observed in 74 patients (57%). The median overall survival in the monogroup was 9 mo and in the cocktail group was 15 mo. If adjusted for prognostic baseline characteristics, the efficacy of both regimens was not significantly different. Conclusion: Deescalated treatment activities of AcPSMA or AcPSMA and LuPSMA cocktail regimens present better tolerability with regard to xerostomia than previous regimens of at least 100 kBq/kg while retaining high antitumor activity in poor-prognosis prostate cancer patients.

Purpose Radiolabeled PSMA-ligands play a major role in today’s nuclear medicine. Since approval of [ 177 Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177 Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99m Tc or therapeutically with 188 Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [ 99m Tc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking. Procedures Two cohorts ( n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [ 99m Tc]Tc-EDDA/HYNIC-iPSMA or [ 99m Tc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden). Results The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [ 99m Tc]Tc-PSMA-GCK01 compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [ 99m Tc]Tc-PSMA-GCK01 vs. median 9.11 [ 99m Tc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [ 99m Tc]Tc-PSMA-GCK01 (0.83) compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands. Conclusions The novel theranostic tracer [ 99m Tc]Tc/[ 188 Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization.

Men diagnosed with aggressive prostate cancer are at high risk of local relapse or systemic progression after definitive treatment. Treatment intensification is highly needed for that patient cohort; however, no relevant stratification tool has been implemented into the clinical work routine so far. Therefore, the aim of the current study was to analyze the role of initial PSMA-PET/CT as a prediction tool for metastases. In total, 335 men with biopsy-proven prostate carcinoma and PSMA-PET/CT for primary staging were enrolled in the present, retrospective study. The number and site of metastases were analyzed and correlated with the maximum standardized uptake value (SUVmax) of the intraprostatic, malignant lesion. Receiver operating characteristic (ROC) curves were used to determine sensitivity and specificity and a model was created using multiple logistic regression. PSMA-PET/CT detected 171 metastases with PSMA-uptake in 82 patients. A statistically significant higher SUVmax was found for men with metastatic disease than for the cohort without distant metastases (median 16.1 vs. 11.2; p < 0.001). The area under the curve (AUC) in regard to predicting the presence of any metastases was 0.65. Choosing a cut-off value of 11.9 for SUVmax, a sensitivity and specificity (factor 1:1) of 76.0% and 58.4% was obtained. The current study confirms, that initial PSMA-PET/CT is able to detect a relatively high number of treatment-naïve men with metastatic prostate carcinoma. Intraprostatic SUVmax seems to be a promising parameter for the prediction of distant disease and could be used for treatment stratification—aspects which should be verified within prospective trials.

Purpose First-line treatment of patients with recurrent, metastatic prostate cancer involves hormone therapy with or without additional systemic therapies. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) allows the detection of oligometastatic disease that may be amenable to image-guided radiotherapy. The current study classifies the type and localization of metastases and the clinical outcome of PSMA-PET/CT-guided radiotherapy to selected metastases. Materials and methods Between 2011 and 2019, 86 patients with recurrent, oligometastatic prostate carcinoma were identified by PSMA-PET/CT and were treated with image-guided radiotherapy of their metastases. Sites of relapse were characterized, and the primary endpoint overall survival (OS), biochemical progression-free survival (bPFS), and androgen deprivation therapy (ADT)-free survival were tabulated. Results In total, 37% of the metastases were bone metastases, 48% were pelvic nodal metastases, and 15% were nodal metastases outside of the pelvis. After PSMA-guided radiotherapy, a biochemical response was detected in 83% of the cohort. A statistically significant decrease in the standard uptake value (SUV) was seen in irradiated metastases. After a median follow-up of 26 months, the 3-year OS and bPFS were 84% and 55%, respectively. The median time of ADT-free survival was 13.5 months. A better clinical outcome was observed for patients receiving concomitant ADT or more than 24 fractions of radiation. Conclusion PSMA-guided radiotherapy is a promising therapeutic approach with excellent infield control for men with oligorecurrent prostate carcinoma. However, prospective, randomized trials are necessary to determine if this approach confers a survival advantage.

For oncologic management or radiotherapy planning, reliable staging tools are essential. The recent development of quinoline-based ligands targeting cancer-associated fibroblasts demonstrated promising preclinical and clinical results. The current study aimed to evaluate the role of fibroblast activation protein inhibitor (FAPI) PET/CT as a first clinical analysis for primary malignancies within the lower gastrointestinal tract (LGT). Methods:68Ga-FAPI PET/CT was performed on a cohort of 22 patients with LGT tumors, including 15 patients with metastatic disease, 1 patient with suspected local relapse, and 6 treatment-naïve patients. Uptake of 68Ga-FAPI-04 and 68Ga-FAPI-46 was quantified by SUVmax and SUVmean After comparison with standard imaging, changes in tumor stage or localization and in oncologic or radiooncologic management were recorded. Results: The highest uptake of FAPI tracer was observed in liver metastases and anal cancer, with an SUVmax of 9.1 and 13.9, respectively. Because of low background activity in normal tissue, there was a high tumor-to-background ratio of more than 3 in most lesions. In treatment-naïve patients, TNM was changed in 50%, whereas in patients with metastases, new findings occurred in 47%. In total, FAPI imaging caused a high, medium, and low change in oncologic or radiooncologic management in 19%, 33%, and 29%, respectively. For almost every patient undergoing irradiation, target volume delineation was improved by 68Ga-FAPI PET/CT. Conclusion: The present study demonstrated that both primary and metastatic LGT tumors were reliably detected by 68Ga-FAPI PET/CT, leading to relevant changes in TNM status and oncologic or radiooncologic management. 68Ga-FAPI PET/CT seems to be a highly promising imaging agent for the diagnosis and management of LGT tumors, potentially opening new applications for tumor staging or restaging.

Introduction: This prospective, non-randomized phase II trial aimed to investigate the role of additional irradiation of the pelvic nodes for patients with prostate cancer and a high risk for nodal metastases using helical intensity-modulated radiotherapy with daily image guidance (IMRT/IGRT). Methods and materials: Between 2009 and 2012, 40 men with treatment-naïve prostate cancer and a risk of lymph node involvement of more than 20% were enrolled in the PLATIN-1 trial. All patients received definitive, helical IMRT of the pelvic nodes (total dose of 51.0 Gy) with a simultaneous integrated boost (SIB) to the prostate (total dose of 76.5 Gy) in 34 fractions. Antihormonal therapy (AHT) was administered for a minimum of 2 months before radiotherapy continuing for at least 24 months. Results: After a median follow-up of 71 months (range: 5-95 months), pelvic irradiation was associated with a 5-year overall survival (OS) and biochemical progression-free survival (bPFS) of 94.3% and 83.6%, respectively. For our cohort, no grade 4 gastrointestinal (GI) and genitourinary (GU) toxicity was observed. Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire was comparable to EORTC reference values without significant changes. Conclusion: The current trial demonstrates that elective IMRT/IGRT of the pelvic nodes with SIB to the prostate for patients with a high-risk of lymphatic spread is safe and shows an excellent clinical outcome without compromising the quality of life. The PLATIN-1 trial delivers eminent baseline data for future studies using modern irradiation techniques.