Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially in diffusion-weighted imaging (DWI), which would be, however, crucial to derive biologically meaningful information. Thus, our aim was to optimize fusion and voxel-wise analyses of DWI and standardized uptake values (SUVs) using a novel software for m2p analyses. Using research software, we evaluated the precision of image co-registration and voxel-wise analyses including the rigid and elastic 3D registration of DWI and [18F]-Fluorodeoxyglucose (FDG)-PET from an integrated PET/MR system. We analyzed DWI distortions with a volume-preserving constraint in three different 3D-printed phantom models. A total of 12 PET/MR-DWI clinical datasets (bronchial carcinoma patients) were referenced to the T1 weighted-DIXON sequence. Back mapping of scatterplots and voxel-wise registration was performed and compared to the non-optimized datasets. Fusion was rated using a 5-point Likert scale. Using the 3D-elastic co-registration algorithm, geometric shapes were restored in phantom measurements; the measured ADC values did not change significantly (F = 1.12, p = 0.34). Reader assessment showed a significant improvement in fusion precision for DWI and morphological landmarks in the 3D-registered datasets (4.3 ± 0.2 vs. 4.6 ± 0.2, p = 0.009). Most pronounced differences were noted for the chest wall (p = 0.006), tumor (p = 0.007), and skin contour (p = 0.014). Co-registration increased the number of plausible ADC and SUV combinations by 25%. The volume-preserving elastic 3D registration of DWI significantly improved the precision of fusion with anatomical sequences in phantom and clinical datasets. The research software allowed for a voxel-wise analysis and visualization of [18F]FDG-PET/MR data as a “combined diffusivity–metabolic index” (cDMI). The clinical value of the optimized PET/MR biomarker can thus be tested in future PET/MR studies.

Due to the increasing use of cross-sectional imaging techniques and new technical possibilities, the number of incidentally detected cystic lesions of the pancreas is rapidly increasing in everyday radiological routines. Precise and rapid classification, including targeted therapeutic considerations, is of essential importance. The new European guideline should also support this. This review article provides information on the spectrum of cystic pancreatic lesions, their appearance, and a comparison of morphologic and histologic characteristics. This is done in the context of current literature and clinical value. The recommendations of the European guidelines include statements on conservative management as well as relative and absolute indications for surgery in cystic lesions of the pancreas. The guidelines suggest surgical resection for mucinous cystic neoplasm (MCN) ≥ 40 mm; furthermore, for symptomatic MCN or imaging signs of malignancy, this is recommended independent of its size (grade IB recommendation). For main duct IPMNs (intraductal papillary mucinous neoplasms), surgical therapy is always recommended; for branch duct IPMNs, a number of different risk criteria are applicable to evaluate absolute or relative indications for surgery. Based on imaging characteristics of the most common cystic pancreatic lesions, a precise diagnostic classification of the tumor, as well as guidance for further treatment, is possible through radiology.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of the elderly, with high metastatic potential and poor prognosis. In particular, the primary resistance to immune checkpoint inhibitors (ICI) in metastatic (m)MCC patients represents a challenge not yet met by any efficient treatment modality. Herein, we describe a novel therapeutic concept with short-interval, low-dose 177Lutetium (Lu)-high affinity (HA)-DOTATATE [177Lu]Lu-HA-DOTATATE peptide receptor radionuclide therapy (SILD-PRRT) in combination with PD-1 ICI to induce remission in patients with ICI-resistant mMCC. We report on the initial refractory response of two immunocompromised mMCC patients to the PD-L1 inhibitor avelumab. After confirming the expression of somatostatin receptors (SSTR) on tumor cells by [68Ga]Ga-HA-DOTATATE-PET/CT (PET/CT), we employed low-dose PRRT (up to six treatments, mean activity 3.5 GBq per cycle) at 3–6 weeks intervals in combination with the PD-1 inhibitor pembrolizumab to restore responsiveness to ICI. This combination enabled the synergistic application of PD-1 checkpoint immunotherapy with low-dose PRRT at more frequent intervals, and was very well tolerated by both patients. PET/CTs demonstrated remarkable responses at all metastatic sites (lymph nodes, distant skin, and bones), which were maintained for 3.6 and 4.8 months, respectively. Both patients eventually succumbed with progressive disease after 7.7 and 8 months, respectively, from the start of treatment with SILD-PRRT and pembrolizumab. We demonstrate that SILD-PRRT in combination with pembrolizumab is safe and well-tolerated, even in elderly, immunocompromised mMCC patients. The restoration of clinical responses in ICI-refractory patients as proposed here could potentially be used not only for patients with mMCC, but many other cancer types currently treated with PD-1/PD-L1 inhibitors.

1328 Aim: The novel PSMA-specific PET-Tracer [F-18]siPSMA-14 showed promising biodistribution and tumour uptake in prostate cancer (PCa) bearing mice. Our aim was to analyze its clinical performance in primary- (PS) and restaging (RS) of PCa patients by analyzing biodistribution, detection rates and interobserver variability at 90min p.i.. Methods: In 134 patients with PCa (69.7 ± 7.5 years; GS 6-9; median (range) PSA 2.36 (0.08-1898) ng/ml) [F-18]siPSMA-14 PET/CT was performed for PS (40%, 54/134) or RS (60%, 80/134). Images were acquired 90min p.i. of 374.2 ± 8.1 MBq without forced diuresis. Findings in different lesion localizations (prostatic lesions (PL), lymphatic lesions (LN), bone lesions (B), visceral lesions (P)) were rated using a 5-scale-system ranging from C1 (definitely benign) to C5 (definitely malignant). Images were evaluated by two nuclear medicine physicians and radiologists (R1, R2). Agreement between R1 and R2 was measured by Cohens-Kappa. Biodistribution measurements were performed using SUVmean in a fixed size region of interest (ROI) to assess the physiological and pathological tracer accumulation. For contrast evaluation target/non target ratios (TTR) were measured by comparing tumour- and background uptake. Results: In consensus reading, the detection rate was 94% (51/54) and 86% (69/80) in PS and RS respectively. In subgroups with PSA values of 0-0.5, 0.5-1, 1-5 and >5 ng/ml detection rates were 68% (19/28), 89% (17/19), 94% (30/32) und 98% (54/55). Interobserver agreement for PL, LN, P was high with Kappa-values of 0.85, 0.75, 0.86 and with 0.51 moderate for B. TTR for PL (n = 88), LN (n = 68), B (n = 51), P (n = 3) were high with 9.3, 11.6, 14.3, 14.6; PL-uptake ranged above urinary bladder uptake with an average SUVmean ratio of 1.7. Conclusions: [F-18]siPSMA-14-PET/CT performs comparably concerning detection rates to other PSMA-binding radiopharmaceuticals with high interobserver agreement and excellent contrast. A major advantage is good performance and image quality adjacent to the urinary bladder even without forced diuresis which is of high relevance for detection of loco-regional tumour recurrence.

Splenosis is a rare disease, which is often discovered incidentally years after surgical procedures on the spleen or traumatic splenic lesions. Through injury of the splenic capsule, splenic cells are able to spread and autoimplant in a fashion similar to the process of metastatic cancer. Here we present the case of a 62-year-old female patient with a palpable tumor of the lower abdomen. Her medical history was unremarkable, except for splenectomy after traumatic splenic lesion in her childhood. Clinical examination and diagnostic imaging raised the suspicion of advanced ovarian cancer, which was further substantiated by the typical presentation of adnexal masses and disseminated peritoneal metastases during the following staging laparotomy. Surprisingly, we also found peritoneal implants macroscopically similar to splenic tissue. Microscopic examination of tissue specimens by intrasurgical frozen section confirmed the diagnosis of intra-abdominal splenosis. The patient then underwent cytoreductive surgery with complete resection of all cancer manifestations, sparing the remaining foci of splenosis to avoid further morbidity. This case demonstrates the rare coincidence of intra-abdominal carcinoma and splenosis, which could lead to intraoperative difficulties by misinterpreting benign splenic tissue. Therefore, splenosis should be considered in patients with medical history of splenic lesions and further diagnostic imaging like Tc-99m-tagged heat-damaged RBC scan could be used for presurgical distinguishing between tumor spread in the abdominal cavity and disseminated splenosis. The presented case report should not only raise awareness for the rare disease splenosis, but also emphasize the need to consider the possibility of simultaneous incidence of benign and malignant intra-abdominal lesions, as to our knowledge this is the first published case of simultaneous peritoneal carcinomatosis and splenosis.

Synergistic effects of immunotherapy with pembrolizumab or drugs targeting DNA damage, such as olaparib, might be used to overcome the limitations of radioligand therapy (RLT) with 177Lu-prostatespecific membrane antigen (PSMA) in metastasized castration-resistant prostate cancer. Here, we present 2 patients receiving such combination or sequential therapies. Methods: RLT was performed at 6- to 8-wk intervals after the patients either exhausted or were considered unfit for all approved conventional treatments. Patient 1 was on pembrolizumab for his squamous cell carcinoma of the skin, whereas patient 2 received RLT sequentially 4 wk after 3 mo of monotherapy with olaparib. Results: Both patients tolerated RLT without any significant hematotoxicity. Patient 2 showed a radiologic and biochemical response, whereas patient 1 achieved prostate-specific antigen stabilization after 3 therapy cycles. Conclusion: These cases indicate that RLT in combination with pembrolizumab or sequentially after olaparib might be well tolerated in single patients.

ZusammenfassungLange beschränkte sich die bildmorphologische Beurteilung von Tumoren auf deren Größe einschließlich der Größendynamik, das Kontrastierungsmuster sowie deren visuell fassbaren Verhalten zum umliegenden Gewebe. In der letzten Dekade rückten zunehmend weitere Aspekte der Bildauswertung von in der klinischen Routine angefertigten Bilddatensätzen in den Fokus, welche dank stetig steigender Prozessorleistung und entsprechend neuer Anwendungsmöglichkeiten erstmals in größerem Umfang analysiert werden konnten. Begriffe wie Tumorheterogenität, „machine learning“ und „big data“ fanden sich immer häufiger in den Überschriften der Publikationen. Es ist gemeinhin anerkannt, dass Tumoren biologisch in der überwiegenden Zahl der Fälle keine homogene Masse darstellen, sondern sowohl auf makroskopischer als auch auf mikroskopischer und genetischer Ebene heterogene Gewebe darstellen. Diese histopathologischen und immunhistochemischen Erkenntnisse mit Tumorarealen unterschiedlicher Zelldichte, Angioneogenese und nekrotischen Anteilen sollten ein entsprechend quantifizierbares Korrelat in den bildgebenden Verfahren aufweisen. Die Heterogenitätsanalyse von Geweben in computertomografischen Datensätzen findet entsprechend in der Onkologie ein breites Anwendungsspektrum, aber auch nicht maligne Erkrankungen stellen einen möglichen Anwendungsbereich für diese Art der Bilddatenauswertung dar. Der nachfolgende Artikel soll eine Übersicht über bereits erfolgte Auswertungen von CT-Datensätzen bei verschiedenen Tumorentitäten und nicht-onkologischen Fragestellungen liefern und die Herausforderungen für die weitere Anwendung von Heterogenitätsanalysen aufzeigen. Ein wichtiges Ziel stellt hierbei die Identifikation von möglichen bildgebenden Biomarkern zur Therapieresponseevaluation dar, um mit entsprechenden Rückschlüssen die Fortführung oder Umstellung der therapeutischen Maßnahmen zu untermauern.