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Aim The recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has yielded very promising results regarding image quality and sensitivity in oncological patients. We, herein, aim to determine an appropriate acquisition time range for the new long axial field of view Biograph Vision Quadra PET/CT (Siemens Healthcare) using low dose [18F]FDG activity in a group of melanoma patients. Methodology Forty-nine melanoma patients were enrolled in the study. All patients underwent total body PET/CT from the top of the head through the feet in two bed positions (field-of-view 106 cm) after i.v. injection of 2.0 MBq/kg [18F]FDG. The PET images of the first bed position (head to upper thigh; PET-10) were reconstructed and further split into 8-min (PET-8), 6-min (PET-6), 5-min (PET-5), 4-min (PET-4), and 2-min (PET-2) duration groups. Comparisons were performed between the different reconstructed scan times with regard to the visual evaluation of the PET/CT scans using the PET-10 images as reference and by calculating the 95%-CI for the differences between different time acquisitions. Moreover, objective evaluation of PET/CT image quality was performed based on SUV calculations of tumor lesions and background, leading to calculation of liver signal-to-noise ratio (SNR), and tumor-to-background ratio (TBR). Results A total of 60 scans were evaluated. Concerning visual analysis, 49/60 (81.7%) PET-10 scans were pathological, while the respective frequencies were 49/60 (81.7%) for PET-8 (95%-CI: − 0.0602–0.0602), 49/60 (81.7%) for PET-6 (95%-CI: − 0.0602–0.0602), 48/60 (80%) for PET-5 (95%-CI: − 0.0445–0.0886), 46/60 (76.7%) for PET-4 (95%-CI: − 0.0132–0.1370), and 45/60 (75%) for PET-2 (95%-CI: 0.0025–0.1593). In 18 PET-10 scans, the extent of metastatic involvement was very large, rendering the accurate calculation of [18F]FDG-avid tumor lesions very complicated. In the remaining 42 PET-10 scans, for which the exact calculation of tumor lesions was feasible, a total of 119 tumor lesions were counted, and the respective lesion detection rates for shorter acquisitions were as follows: 97.5% (116/119) for PET-8 (95%-CI: 0–1), 95.0% (113/119) for PET-6 (95%-CI: 0–1), 89.9% (107/119) for PET-5 (95%-CI: 0–2), 83.2% (99/119) for PET-4 (95%-CI: 1–2), and 73.9% (88/119) for PET-2 (95%-CI: 2–4). With regard to objective image quality evaluations, as a general trend, the reduction of acquisition time was associated with a decrease of liver SNR and a decrease of TBR, although in lesion-based analysis the change in TBR and tumor SUVmean values was non-significant up to 6 and 5 min acquisitions, respectively. Conclusions In melanoma, low-dose LAFOV PET/CT imaging is feasible and can reduce the total scan time from head to upper thigh up to 5 min providing comparable diagnostic data to standard lengths of acquisition. This may have significant implications for the diagnostic work-up of patients with melanoma, given the need for true whole-body imaging in this type of cancer.

Purpose To investigate the prognostic value of [18F]FDG PET/CT as part of response monitoring in metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs). Methods Sixty-seven patients underwent [18F]FDG PET/CT before start of treatment (baseline PET/CT), after two cycles (interim PET/CT) and after four cycles of ICIs administration (late PET/CT). Metabolic response evaluation was based on the conventional EORTC and PERCIST criteria, as well as the newly introduced, immunotherapy-modified PERCIMT, imPERCIST5 and iPERCIST criteria. Metabolic response to immunotherapy was classified according to four response groups (complete metabolic response [CMR], partial metabolic response [PMR], stable metabolic disease [SMD], progressive metabolic disease [PMD]), and further dichotomized by response rate (responders = [CMR] + [PMR] vs. non-responders = [PMD] + [SMD]), and disease control rate (disease control = [CMR] + [PMR] + [SMD] vs. [PMD]). The spleen-to-liver SUV ratios (SLRmean, SLRmax) and bone marrow-to-liver SUV ratios (BLRmean, BLRmax) were also calculated. The results of PET/CT were correlated with patients’ overall survival (OS). Results Median patient follow up [95% CI] was 61.5 months [45.3 – 66.7 months]. On interim PET/CT, the application of the novel PERCIMT demonstrated significantly longer survival for metabolic responders, while the rest criteria revealed no significant survival differences between the different response groups. Respectively on late PET/CT, both a trend for longer OS and significantly longer OS were observed in patients responding to ICIs with metabolic response and disease control after application of various criteria, both conventional and immunotherapy-modified. Moreover, patients with lower SLRmean values demonstrated significantly longer OS. Conclusion In patients with metastatic melanoma PET/CT-based response assessment after four ICIs cycles is significantly associated with OS after application of different metabolic criteria. The prognostic performance of the modality is also high after the first two ICIs cycles, especially with employment of novel criteria. In addition, investigation of spleen glucose metabolism may provide further prognostic information.

Long axial field of view (LAFOV) PET-CT scanners have been recently developed and are already in clinical use in few centers worldwide. Although still limited, the hitherto acquired experience with these novel systems highlights an increased sensitivity as their main advantage, which results in an increased lesion detectability. This attribute, alternatively, allows a reduction in PET acquisition time and/or administered radiotracer dose, while it renders delayed scanning of satisfying diagnostic accuracy possible. Another potential advantage of the new generation scanners is CT-less approaches for attenuation correction with the impact of marked reduction of radiation exposure, which may in turn lead to greater acceptance of longitudinal PET studies in the oncological setting. Further, the possibility for the first time of whole-body dynamic imaging, improved compartment modeling, and whole-body parametric imaging represent unique characteristics of the LAFOV PET-CT scanners. On the other hand, the advent of the novel LAFOV scanners is linked to specific challenges, such as the high purchase price and issues related to logistics and their optimal operation in a nuclear medicine department. Moreover, with regard to its research applications in oncology, the full potential of the new scanners can only be reached if different radiopharmaceuticals, both short and long-lived ones, as well as novel tracers, are available for use, which would, in turn, require the appropriate infrastructure in the area of radiochemistry. Although the novel LAFOV scanners are not yet widely used, this development represents an important step in the evolution of molecular imaging. This review presents the advantages and challenges of LAFOV PET-CT imaging for oncological applications with respect to static and dynamic acquisition protocols as well as to new tracers, while it provides an overview of the literature in the field.

Nuclear medicine imaging modalities, and in particular positron emission tomography (PET), provide functional images that demonstrate the mean radioactivity distribution at a defined point in time. With the help of mathematical model's, it is possible to depict isolated parameters of the radiotracers' pharmacokinetics and to visualize them. These so called parametric images add a new dimension to the existing conventional PET images and provide more detailed information about the tracer distribution over time and space. Prerequisite for the calculation of parametric images, which reflect specific pharmacokinetic parameters, is the dynamic PET (dPET) data acquisition. Hitherto, PET parametric imaging has mainly found use for research purposes. However, it has not been yet implemented into clinical routine, since it is more time-consuming, it requires a complicated analysis and still lacks a clear benefit over conventional PET imaging. However, the recent introduction of new PET-CT scanners with an ultralong field of view, which allow a faster data acquisition and are associated with higher sensitivity, as well as the development of more sophisticated evaluation software packages will probably lead to a renaissance of dPET and parametric maps even of the whole body. The implementation of dPET imaging in daily routine with appropriate acquisition protocols, as well as the calculation, interpretation and potential clinical applications of parametric images will be discussed in this review article.

A 73-year-old man with multiple myeloma (initial diagnosis 21 months earlier) was referred to our center for a whole-body 18 F-FDG PET/CT. We detected a bilateral synchronous testicular manifestation, which was confirmed by histopathology after orchiectomy. Besides hypermetabolic lesions in the spine and ribs (most likely old fractures), known osteolysis showed no uptake. Extramedullary manifestation occurs in 13% to 20% of cases, among these 4% demonstrate testicular manifestation, which is associated with poor survival rates. Optimal therapy management is still unclear, due to limited data. To the authors' knowledge, so far only 3 comparable cases have been described.

Purpose [68 Ga]Ga-PSMA-11 is a promising radiopharmaceutical for detecting tumour lesions in prostate cancer, but knowledge of the pharmacokinetics is limited. Dynamic PET-CT was performed to investigate the tumour detection and differences in temporal distribution, as well as in kinetic modelling of [68 Ga]Ga-PSMA-11 by tissue type. Methods Dynamic PET-CT over the lower abdomen and static whole-body PET-CT 80–90 min p.i. from 142 patients with biochemical recurrence were retrospectively analysed. Detection rates were compared to PSA levels. Average time-activity curves were calculated from tumour lesions and normal tissue. A three-compartment model and non-compartment model were used to calculate tumour kinetics. Results Overall detection rate was 70.42%, and in patients with PSA > 0.4 ng/mL 76.67%. All tumour lesions presented the steepest standardised uptake value (SUV) incline in the first 7–8 min before decreasing to different degrees. Normal tissue presented with a low uptake, except for the bladder, which accumulated activity the steepest 15–16 min. p.i.. While all tumour lesions continuously increased, bone metastases showed the steepest decline, resulting in a significantly lower SUV than lymph node metastases (60 and 80–90 min). Transport rate from the blood and tracer binding and internalisation rate were lower in bone metastases. Heterogeneity (fractal dimension) and vascular density were significantly lower in bone metastases. Conclusion Even at low PSA between 0.51 and 0.99 ng/mL, detection rate was 57%. Dynamic imaging showed a time window in the first 10 min where tumour uptake is high, but no bladder activity is measured, aiding accuracy in distinction of local recurrence. Kinetic modelling provided additional information for tumour characterisation by tissue type.

A new organic material with three 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene dyes (BODIPYs) at the periphery of the central core is successfully synthesized (3BDP3T) and its corresponding aqueous nanoparticles are prepared via the encapsulation approach and characterized in detail both experimentally and theoretically with the aid of the Density Functional Theory (DFT). The linear and non-linear optical properties of the synthesized material are also studied. Until now, the development of organic materials with three BODIPYs as substituents is limited and their properties are not fully resolved. The obtained 3BDP3T-based nanoparticles exhibit far-red and near infrared (NIR) emission with photoluminescence quantum yields of 0.021, which is promising as a new fluorescent contrast agent in the far-red and NIR spectral regions.

Conjugated polymer nanoparticles (CPNs) have emerged as a new promising class of cancer theranostic agents due to their desirable optical features, such as high absorption coefficient and photoluminescence quantum yields, spanning from the ultraviolet to the near infrared, along with their photothermal and photodynamic properties. However, limited studies have been demonstrated up to now on the rational design of CPNs for specific biological purposes. In particular, it is not well understood how exactly the chemical structure of the conjugated polymer and the nanoparticle formulation approach (encapsulation versus nanoprecipitation) associates with the cytotoxicity, the intracellular uptake in vitro and the therapeutic behavior. For this reason, nanoprecipitated and encapsulated aqueous CPNs were formulated consisting of thiophene–quinoxaline type conjugated polymers varying as regards the number of the fluorine atoms (three versus four) on the repeat unit. The obtained CPNs were systematically examined in terms of cytotoxicity and intracellular uptake in vitro in three epithelial breast cell lines represented by one normal cell line, and two breast cancer cell lines composed of one luminal and one triple negative line. From the obtained results, it is presented that only the nanoprecipitated CPNs with the three fluorine atoms exhibited efficient intracellular uptake to all the epithelial cell lines tested, in addition to the visible fluorescence on the triple negative breast cancer cells. Moreover, evaluation of the comparison of the effect of the CPNs on cell proliferation and apoptosis of all cell lines with the corresponding antibiotic staurosporine was performed, indicating a putative therapeutic potential of nanoparticles under study.

Purpose In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [18F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment. Methods Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [18F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients’ response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Patients were further grouped into two groups: those demonstrating metabolic benefit (MB), including patients with SMD, PMR, and CMR, and those demonstrating no MB (no-MB), including patients with PMD. Moreover, patterns of [18F]FDG uptake suggestive of radiologic immune-related adverse events (irAEs) were documented. Progression-free survival (PFS) was measured from the date of interim PET/CT until disease progression or death from any cause. Results Median follow-up from interim PET/CT was 24.2 months (19.3–41.7 months). According to the EORTC criteria, 14 patients showed MB (1 CMR, 6 PMR, and 7 SMD), while 11 patients showed no-MB (PMD). Respectively, the application of the PERCIMT criteria revealed that 19 patients had MB (1 CMR, 6 PMR, and 12 SMD), and 6 of them had no-MB (PMD). With regard to PFS, no significant difference was observed between patients with MB and no-MB on interim PET/CT according to the EORTC criteria (p = 0.088). In contrary, according to the PERCIMT criteria, patients demonstrating MB had a significantly longer PFS than those showing no-MB (p = 0.045). The emergence of radiologic irAEs (n = 11 patients) was not associated with a significant survival benefit. Regarding the sub-cohort undergoing also a third PET/CT, 14/17 patients (82%) showed concordant responses and 3/17 (18%) had a mismatch of response assessment between interim and late PET/CT. Conclusion PET/CT-based response of metastatic melanoma to PD-1 blockade after application of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results.

Recent efforts in the field of organic photodetectors (OPD) have been focused on extending broadband detection into the near-infrared (NIR) region. Here, two blends of an ultralow bandgap push–pull polymer TQ-T combined with state-of-the-art non-fullerene acceptors, IEICO-4F and Y6, are compared to obtain OPDs for sensing in the NIR beyond 1100 nm, which is the cut off for benchmark Si photodiodes. It is observed that the TQ-T:IEICO-4F device has a superior IR responsivity (0.03 AW-1 at 1200 nm and −2 V bias) and can detect infrared light up to 1800 nm, while the TQ-T:Y6 blend shows a lower responsivity of 0.01 AW-1. Device physics analyses are tied with spectroscopic and morphological studies to link the superior performance of TQ-T:IEICO-4F OPD to its faster charge separation as well as more favorable donor–acceptor domains mixing. In the polymer blend with Y6, the formation of large agglomerates that exceed the exciton diffusion length, which leads to high charge recombination, is observed. An application of these devices as biometric sensors for real-time heart rate monitoring via photoplethysmography, utilizing infrared light, is demonstrated.

The development of new aqueous conjugated polymer nanoparticles with high photoluminescence quantum yields (PLQYs) at the far red and near infrared (NIR) spectral regions (>650 nm) as alternative polymer probes for fluorescence imaging is reported. This is achieved through an appropriate chemical design by the introduction of up to four fluorine atoms in the different positions of a donor–acceptor (D–A) polymer backbone consisting of thiophene as the electron donating unit and quinoxaline as the electron withdrawing building block. The resulting series of low synthetic complexity conjugated polymers enable us to perform a detailed structure–properties relationship study between the synthesized conjugated polymers and their corresponding aqueous nanoparticles as prepared by the nanoprecipitation and encapsulation methods. We manage to achieve PLQY for aqueous NIR conjugated polymer probes of 0.1 and a PLQY of 0.18 for the far-red emitting conjugated polymer probes. Furthermore, our work paves the way for the rational design of new conjugated polymers with enhanced PLQY, especially in the NIR spectral region, through better control of the intramolecular and intermolecular polymer chain interactions.

Imaging plays a pivotal role in the management of multiple myeloma (MM). Besides morphological imaging methods, such as whole-body X‑ray, computed tomography (CT) and magnetic resonance imaging (MRI), the hybrid modality positron emission tomography/CT (PET/CT) using the glucose analogueAim of this review article is to outline the major applications of PET/CT in the diagnosis and management of MM, and to provide hints on the reading and interpretation.Background knowledge and guideline recommendations on imaging of MM are outlined and complemented by recent study results.AlthoughPET/CT has a high value in the diagnosis, prognosis, and assessment of treatment response in patients with MM. Therefore, the role of the modality in the management of the disease is expected to increase in the near future.HINTERGRUND: Die Bildgebung spielt beim Management des multiplen Myeloms (MM) eine zentrale Rolle. Neben morphologischen Bildgebungsmethoden, wie Ganzkörper-Röntgenaufnahme (Pariser Schema), Computertomographie (CT) und Magnetresonanztomographie (MRT), wird zunehmend die Positronen-Emissions-Tomographie/CT (PET/CT) unter Verwendung vonZiel dieses Übersichtsartikels ist es, die wichtigsten Anwendungen der PET/CT in der Diagnose und Behandlung des MM zu beschreiben und Hinweise zu deren Auswertung zu geben.Hintergrundwissen und Leitlinienempfehlungen zur PET-basierten Bildgebung des MM werden erläutert und durch aktuelle Studienergebnisse ergänzt.DieDie PET/CT hat einen hohen Stellenwert bei der Diagnose, Prognose und Bewertung des Therapieansprechens von MM. Daher wird erwartet, dass die Rolle dieser Modalität beim Management der Krankheit in naher Zukunft noch weiter zunehmen wird.

Simple Summary The fractal dimension (FD) and the multifractal spectrum (MFS) are nonlinear quantitative measures which express the heterogeneity in the distribution of the tracer, F-18-fluorodeoxyglucose, (18F-FDG), in the body of patients suffering from metastatic melanoma. Given the well-documented, high accumulation of the tracer in tumor/metastatic sites, the measures expressing the tracer distribution also express the extent of metastases in the body. As such, FD and MFS can be employed to detect the presence of melanoma and to monitor the therapeutic outcome using the PET-CT follow-up digitized scans of the patients. In the present study, the FD and MFS measures of patients are evaluated before and during treatment with PD-1 inhibitors and are compared with the corresponding values of healthy controls. The MFS predictions agree with the PET Response Evaluation Criteria for Immunotherapy (PERCIMT) in 81% of the cases, while the FD agrees in 77% of all cases. Therefore, the quantitative MFS is proposed as an additional, alternative biomarker for monitoring the immunotherapy outcome in melanoma patients, after treatment with PD-1 inhibitors. Abstract Longitudinal whole-body PET-CT scans with F-18-fluorodeoxyglucose (18F-FDG) in patients suffering from metastatic melanoma were analyzed and the tracer distribution in patients was compared with that of healthy controls. Nineteen patients with metastatic melanoma were scanned before, after two and after four cycles of treatment with PD-1 inhibitors (pembrolizumab, nivolumab) applied as monotherapy or as combination treatment with ipilimumab. For comparison eight healthy controls were analyzed. As quantitative measures for the comparison between controls and patients, the nonlinear fractal dimension (FD) and multifractal spectrum (MFS) were calculated from the digitized PET-CT scans. The FD and MFS measures, which capture the dispersion of the tracer in the body, decreased with disease progression, since the tracer particles tended to accumulate around metastatic sites in patients, while the measures increased when the patients’ clinical condition ameliorate. The MFS measure gave better predictions and were consistent with the PET Response Evaluation Criteria for Immunotherapy (PERCIMT) in 81% of the cases, while FD agreed in 77% of all cases. These results agree, qualitatively, with a previous study of our group when treatment with ipilimumab monotherapy was considered.

Aim: Autoimmune colitis is a typical and possible severe side effect among patients treated with ipilimumab. Patients & methods: We prospectively included 100 patients with metastasized melanoma under ipilimumab treatment in a radiological study of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). PET evidence of pancolitis (‘PET-colitis’) was correlated with clinical variables. Results: We observed a significant correlation between PET-colitis and clinically significant diarrhoea, although PET-colitis was more frequent (49 vs 29% of patients, respectively). Neither PET-colitis nor diarrhoea was significantly correlated with response to therapy. Other immune-related adverse events, however, such as hypophysitis and hepatitis were associated with response to therapy and overall survival. Conclusion: Increased 18F-FDG uptake in the colon correlated with clinical symptoms but did not predict clinical outcome to ipilimumab.

Preoperative devascularization might improve local control and thus the outcome of patients with soft tissue sarcoma (STS). The multikinase inhibitor pazopanib has antiangiogenic effects and is approved for treating metastatic STS. We conducted a trial of preoperative pazopanib therapy in high-risk STS. This single-arm, phase II trial included patients with resectable, non-metastatic, treatment-naive, high-risk STS. Patients received pazopanib 800 mg daily while waiting for surgery (21-day ‘window of opportunity’). The primary endpoint was metabolic response rate (MRR; proportion of patients with ≥ 50% reduction of mean standardized uptake value [SUVmean] in post- vs. pretreatment fluorodeoxyglucose–positron emission tomography/computed tomography [FDG-PET-CT]). Planned sample size was 35 patients (type I error, 5%; type II error, 20%). A translational substudy explored associations between response and concentration of circulating angiogenic factors. Futility analysis was performed after 21 patients (11 female, mean age 67 years; liposarcoma n = 15); 17/21 patients were evaluable for the primary endpoint. The MRR was 1/17 (5.9%, 95% confidence interval

Although the presence of focal lesions in 18F-fluo-rodeoxygluocse (FDG) positron emission tomography (PET)/computed tomography (CT) is associated with adverse outcome in multiple myeloma, data on diffuse bone marrow infiltration are lacking. In the current prospective study we investigated the

Purpose Transcriptomic profiling has enabled the neater genomic characterization of several cancers, among them colorectal cancer (CRC), through the derivation of genes with enhanced causal role and informative gene sets. However, the identification of small-sized gene signatures, which can serve as potential biomarkers in CRC, remains challenging, mainly due to the great genetic heterogeneity of the disease. Methods We developed and exploited an analytical framework for the integrative analysis of CRC datasets, encompassing transcriptomic data and positron emission tomography (PET) measurements. Profiling data comprised two microarray datasets, pertaining biopsy specimen from 30 untreated patients with primary CRC, coupled by their F-18-Fluorodeoxyglucose (FDG) PET values, using tracer kinetic analysis measurements. The computational framework incorporates algorithms for semantic processing, multivariate analysis, data mining and dimensionality reduction. Results Transcriptomic and PET data feature sets, were evaluated for their discrimination performance between primary colorectal adenocarcinomas and adjacent normal mucosa. A composite signature was derived, pertaining 12 features: 7 genes and 5 PET variables. This compact signature manifests superior performance in classification accuracy, through the integration of gene expression and PET data. Conclusions This work represents an effort for the integrative, multilayered, signature-oriented analysis of CRC, in the context of radio-genomics, inferring a composite signature with promising results for patient stratification., Graphical Abstract Unlabelled Image

Checkpoint inhibitors have revolutionized the treatment of patients with metastasized melanoma. However, it remains unclear when to stop treatment. We retrospectively analyzed 45 patients (median age 64 years, 58% male) with metastasized melanoma from 3 cancer centers that received checkpoint inhibitors and discontinued therapy due to either immune-related adverse events or patient decision after an (18F)2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) combined with a low-dose CT scan (FDG-PET-CT) scan without signs for disease progression. After a median of 21 (range 1–42) months of immunotherapy an FDG-PET-CT scan was performed to evaluate disease activity. In these, 32 patients (71%) showed a complete metabolic response (CMR) and 13 were classified as non-CMR. After a median follow-up of 34 (range 1–70) months, 3/32 (9%) of CMR patients and 6/13 (46%) of non-CMR patients had progressed (p = 0.007). Progression-free survival (PFS), as estimated from the date of last drug administration, was significantly longer among CMR patients than non-CMR (log-rank: p = 0.001, hazard ratio: 0.127, 95% CI: 0.032–0.511). Two-year PFS was 94% among CMR patients and 62% among non-CMR patients. Univariable Cox regression showed that metabolic response was the only parameter which predicted PFS (p = 0.004). Multivariate analysis revealed that metabolic response predicted disease progression (p = 0.008). In conclusion, our findings suggest that patients with CMR in an FDG-PET-CT scan may have a favorable outcome even if checkpoint inhibition is discontinued.

Background: Neoadjuvant imatinib mesylate (IM) for advanced, non-metastatic gastrointestinal stromal tumors (GIST) of stomach is recommended to downsize the tumor prompting less-extensive operations and preservation of organ function. Methods: We analyzed the clinical-histopathological profile and oncological outcome of 55 patients (median age 58.2 years, range, 30–86 years) with biopsy-proven, cM0, gastric GIST who underwent IM therapy followed by surgery with a median follow-up of 82 months. Results: Initial median tumor size was 113 mm (range, 65–330 mm) and 10 patients started with acute upper GI bleeding. After a median 10 months (range, 2–21 months) of treatment, tumor size had shrunk to 62 mm (range, 22–200 mm). According to Response Evaluation Criteria In Solid Tumors version 1.0 and version 1.1 (RECIST 1.1), 39 (75%) patients had partial response and 14 patients had stable disease, with no progressive disease. At plateau response, 50 patients underwent surgery with an R0 resection rate of 94% and pathological complete response in 24%. In 12 cases (24%), downstaging allowed laparoscopic resection. The mean recurrence-free survival (RFS) was 123 months (95%CI, 99–147) and the estimated 5-year RFS was 84%. Conclusions: Neoadjuvant IM allowed stomach preservation in 96% of our patients with excellent long-term RFS, even when starting treatment during an episode of upper GI bleeding. Preservation of the stomach provides the physiological basis for the use of oral IM in the adjuvant or metastatic setting.

Simple Summary There is currently no consensus on a widely accepted algorithm for imaging Merkel cell carcinoma (MCC) patients. Baseline, tomographic imaging is not generally recommended in early-stage disease, but its value in locally advanced and/or distant metastatic MCC has been well established. In this context, the hybrid imaging modality positron emission tomography/computed tomography (PET/CT) is increasingly applied in the workup of metastatic or unresectable MCC, providing essential information for staging, restaging, and treatment monitoring of the disease. Although the role of PET/CT in the management of loco-regional MCC is still limited and less well-defined, current evidence suggests its important contribution also in cases of localized MCC. Herein, we provide a structured literature review summarizing the most important studies on the role of PET or PET/CT with different radiopharmaceuticals in the clinical care of MCC. Abstract Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy usually arising as a nonspecific nodule on sun-exposed areas of the head and neck. Given the poor prognosis of this aggressive tumor, assessment of disease burden in pre- and post-treatment care may ensure an optimal management with significant implications for patient surveillance and prognosis. Although imaging has established its role in locally advanced or distant metastatic MCC, a standard imaging algorithm is yet to be determined and respective recommendations are mainly based on melanoma. Positron emission tomography/computed tomography (PET/CT) is increasingly evolving as a valuable imaging tool in metastatic or unresectable MCC, mostly utilizing the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) as a radiotracer. Despite being inferior in detecting the disease in its early stages compared to the “gold standard” of sentinel lymph node biopsy, recent evidence suggests an important role for 18F-FDG PET/CT in the routine workup of localized MCC. Moreover, 68Ga-labeled somatostatin analogues have been employed as PET tracers in the field of MCC with promising, yet comparable to 18F-FDG, results. This article provides a structured literature review of the most important studies investigating the role of PET or PET/CT in the clinical practice of MCC.

Introduction: BRAF inhibitors (BRAFi), commonly used in BRAF-mutated metastatic melanoma (MM) treatment, frequently cause arthralgia. Although this is one of the most common side effects, it has not been characterized yet. Methods: We retrospectively included all patients treated with BRAFi +/&minus, MEK inhibitors (MEKi) for MM at the National Center for Tumor Diseases (Heidelberg) between 2010 and 2018 and reviewed patient charts for the occurrence and management of arthralgia. The evaluation was supplemented by an analysis of frozen sera. Results: We included 154 patients (63% males), 31% (48/154) of them reported arthralgia with a median onset of 21 days after the start of the therapy. Arthralgia mostly affected small joints (27/36, 75%) and less frequently large joints (19/36, 53%). The most commonly affected joints were in fingers (19/36, 53%), wrists (16/36, 44%), and knees (12/36, 33%). In 67% (24/36) of the patients, arthralgia occurred with a symmetrical polyarthritis, mainly of small joints, resembling the pattern typically observed in patients affected by rheumatoid arthritis (RA), for which a role of the MAPK signaling pathway was previously described. Patients were negative for antinuclear antibodies, anti-citrullinated protein antibodies, and rheumatoid factor, arthritis was visible in 10 of 13 available PET&ndash, CT scans. The development of arthralgia was linked to better progression-free survival and overall survival. Conclusion: Arthralgia is a common side effect in patients receiving BRAFi +/&minus, MEKi therapy and often presents a clinical pattern similar to that observed in RA patients. Its occurrence was associated with longer-lasting tumor control.

Purpose In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [18F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment. Methods Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [18F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients’ response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Patients were further grouped into two groups: those demonstrating metabolic benefit (MB), including patients with SMD, PMR, and CMR, and those demonstrating no MB (no-MB), including patients with PMD. Moreover, patterns of [18F]FDG uptake suggestive of radiologic immune-related adverse events (irAEs) were documented. Progression-free survival (PFS) was measured from the date of interim PET/CT until disease progression or death from any cause. Results Median follow-up from interim PET/CT was 24.2 months (19.3–41.7 months). According to the EORTC criteria, 14 patients showed MB (1 CMR, 6 PMR, and 7 SMD), while 11 patients showed no-MB (PMD). Respectively, the application of the PERCIMT criteria revealed that 19 patients had MB (1 CMR, 6 PMR, and 12 SMD), and 6 of them had no-MB (PMD). With regard to PFS, no significant difference was observed between patients with MB and no-MB on interim PET/CT according to the EORTC criteria (p = 0.088). In contrary, according to the PERCIMT criteria, patients demonstrating MB had a significantly longer PFS than those showing no-MB (p = 0.045). The emergence of radiologic irAEs (n = 11 patients) was not associated with a significant survival benefit. Regarding the sub-cohort undergoing also a third PET/CT, 14/17 patients (82%) showed concordant responses and 3/17 (18%) had a mismatch of response assessment between interim and late PET/CT. Conclusion PET/CT-based response of metastatic melanoma to PD-1 blockade after application of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-020-05137-7.

Dynamic PET (dPET) studies have been used until now primarily within research purposes. Although it is generally accepted that the information provided by dPET is superior to that of conventional static PET acquisitions acquired usually 60 min post injection of the radiotracer, the duration of dynamic protocols, the limited axial field of view (FOV) of current generation clinical PET systems covering a relatively small axial extent of the human body for a dynamic measurement, and the complexity of data evaluation have hampered its implementation into clinical routine. However, the development of new-generation PET/CT scanners with an extended FOV as well as of more sophisticated evaluation software packages that offer better segmentation algorithms, automatic retrieval of the arterial input function, and automatic calculation of parametric imaging, in combination with dedicated shorter dynamic protocols, will facilitate the wider use of dPET. This is expected to aid in oncological diagnostics and therapy assessment. The aim of this review is to present some general considerations about dPET analysis in oncology by means of kinetic modeling, based on compartmental and noncompartmental approaches, and parametric imaging. Moreover, the current clinical applications and future perspectives of the modality are outlined.

An association between immune-related adverse events (irAEs) caused by immunotherapeutic agents and the clinical benefit of immunotherapy has been suggested. We retrospectively evaluated by means of 18F-FDG PET/CT lymphoid tissue changes in the mediastinal/hilar lymph nodes and the spleen in response to ipilimumab administration in metastatic melanoma. A total of 41 patients with unresectable metastatic melanoma underwent 18F-FDG PET/CT before the start of ipilimumab (baseline PET/CT), after two cycles (interim PET/CT) and at the end of treatment (late PET/CT). Data analysis was focused on the mediastinal/hilar lymph nodes and the spleen. The patients’ best clinical response (BCR) was used as reference. According to the BCR reference, 31 patients showed disease control (DC) and 10 patients showed progressive disease (PD). Mediastinal/hilar lymph node evaluation revealed that in total 4 patients in the interim or late PET/CT (10%) demonstrated a ‘sarcoid-like lymphadenopathy’ as response to treatment (LN-positive). All LN-positive patients responded to ipilimumab with DC. On the other hand, no significant differences between the DC and PD groups regarding both semi-quantitative and quantitative 18F-FDG PET spleen-related parameters at baseline and as response to treatment were detected. Based on our findings, 10% patients in the interim or late PET/CT showed ‘sarcoid-like lymphadenopathy’ as response to treatment. All these patients showed disease control, implying a relation between the appearance of sarcoid-like lymphadenopathy and the clinical benefit of anti-CTLA-4 therapy. On the other hand, quantitative 18F-FDG PET analysis of the spleen showed a poor performance in predicting clinical benefit to ipilimumab.

Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography-computed tomography (PET-CT) with 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on 18F-FDG PET-CT. The classical criteria used for therapy monitoring with 18F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with 18F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the 18F-FDG images for response assessment. Finally, the definition of 18F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.