CT in Patients With External Fixation for Complex Lower Extremity Fractures: Impact of Iterative Metal Artifact Reduction Techniques on Metal Artifact Burden and Subjective Quality.

BACKGROUND. Lower extremity external fixators have complex geometries that induce pronounced metal artifact on CT. Iterative metal artifact reduction (iMAR) algorithms help reduce such artifact, although no dedicated iMAR preset exists for external fixators. OBJECTIVE. The purpose of our study was to compare iMAR presets for CT examinations in terms of quantitative metal artifact burden and subjective image quality in patients with external fixators for complex lower extremity fractures. METHODS. This retrospective study included 72 CT examinations in 56 patients (20 women, 36 men; mean age, 56 ± 18 [SD] years) with lower extremity external fixators (regular, hybrid, or monotube). Examinations were reconstructed without iMAR (hereafter referred to as "noMAR") and with three iMAR presets (iMARspine, iMARhip, iMARextremity). A radiology resident quantified metal artifact burden using software. Two radiology residents independently assessed overall image quality and diagnostic confidence using 4-point scales (4 = excellent [highest quality or highest confidence]). Techniques were compared using Bonferroni-corrected post hoc tests. Interreader agreement was assessed by intraclass correlation coefficients (ICCs). A post hoc multinomial regression model was used for predicting overall image quality. RESULTS. Mean quantitative metal artifact burden was 100,816 ± 45,558 for noMAR, 88,889 ± 44,028 for iMARspine, 82,295 ± 41,983 for iMARhip, and 81,956 ± 41,890 for iMARextremity. Overall image quality yielded an ICC of 0.94 or greater. Using pooled reader data, median overall image quality score for the regular fixator was 2 (noMAR), 3 (iMARspine and iMARhip), and 4 (iMARextremity); for the hybrid fixator, 1 (noMAR), 2 (iMARspine), and 3 (iMARhip and iMARextremity); and for the monotube fixator, 2 (noMAR), 3 (iMARspine and iMARhip), and 4 (iMARextremity). Metal artifact burden was lower and overall image quality was higher (p < .05) for iMARhip and iMARextremity than noMAR and iMARspine for all fixators (aside from image quality of iMARhip and iMARextremity vs iMARspine for regular fixators) but were not different (all, p > .05) between iMARhip and iMARextremity. Median diagnostic confidence was 4 for all fixators and reconstructions. Independent predictors of overall quality relative to noMAR were iMARspine (odds ratio [OR] = 1.92-5.51), iMARhip (OR = 5.56-31.10), and iMARextremity (OR = 7.07-38.21). All iMAR presets introduced new reconstruction artifacts for all examinations for both readers. CONCLUSION. For the three fixator types, iMARhip and iMARextremity achieved greatest metal artifact burden reduction and highest subjective image quality, although both introduced new reconstruction artifacts. CLINICAL IMPACT. CT using the two identified iMAR presets may facilitate perioperative management of external fixators.

Role of computed tomography texture analysis using dual-energy-based bone marrow imaging for multiple myeloma characterization: comparison with histology and established serologic parameters.

OBJECTIVE: To identify textural features on dual-energy CT (DECT)-based bone marrow images in myeloma which correlate with serum markers of myeloma activity and the degree of medullary involvement. METHODS: A total of 110 patients (63.0 ± 11.0 years, 51 female) who underwent unenhanced whole-body DECT between September 2015 and February 2019 were retrospectively included, which was approved by our institutional ethics committee with a waiver of the informed consent requirement. All patients had current hematologic laboratory tests. Using DECT post-processing, non-calcium bone marrow images were reconstructed. The vertebral bodies T10-L5 were segmented for quantification of textural features, which were compared with serologic parameters and myeloma stages by the Mann-Whitney U test. In a subgroup of 56/110 patients with current bone marrow biopsies, textural features were correlated with the degree of bone marrow infiltration. RESULTS: First-order features were higher in patients with advanced stage of myeloma (p < .02), whereas the 2nd-order "gray-level co-occurrence matrix (GLCM) cluster prominence" was lower (p < .04). In patients with elevated serum-free light chains (SFLC) or kappa/lambda SFLC ratio above 1.56, the "entropy" and 2nd-order GLCM features were lower (p < .03). The degree of bone marrow infiltration correlated with 1st-order features (e.g., "uniformity"; rP = 0.49; p < .0001), whereas "entropy" and 2nd-order GLCM features were negatively correlated (e.g., "difference entropy"; rP = - 0.54; p < .0001). CONCLUSIONS: CT textural features applied on non-calcium bone marrow images correlate well with myeloma-related serologic parameters and histology showing a more uniform tissue structure and higher attenuation with increasing medullary infiltration and could therefore be used as additional imaging biomarkers for non-invasive assessment of medullary involvement. KEY POINTS: • Texture analysis applied on dual-energy reconstructed non-calcium bone marrow images provides information about marrow structure and attenuation. • Myeloma-related serologic parameters and the degree of myeloma cell infiltration correlate with 1st- and 2nd-order features which could be useful as additional imaging biomarkers for non-invasive assessment of medullary involvement.

Impact of PET/CT on clinical management in patients with cancer of unknown primary-a PET/CT registry study.

OBJECTIVE: To evaluate the impact of PET/CT on clinical management in patients with cancer of unknown primary (CUP). METHODS: A cohort of patients with CUP undergoing PET/CT was prospectively enrolled in a local PET/CT registry study between April 2013 and June 2018. Questionnaire data from referring physicians on intended patient management prior and after PET/CT were recorded including items on the intended treatment concept and intended additional diagnostics. Changes in management after PET/CT were recorded. Patient outcome of different cohorts was analyzed for overall survival drawn from patient records. RESULTS: One hundred fifty-five patients (53 female; 63.4 ± 12.1 years) were included. Intended therapeutic management was revised in 45.8% of patients after PET/CT, including major changes affecting the intended treatment goal in 26.5% of patients and minor changes (therapy adjustments) in 19.3% of patients. Invasive and additional diagnostic procedures were intended in 25.8% and 63.2% prior PET/CT and 13.5% and 6.5% after PET/CT. PET/CT-based curative therapy concepts were associated with significantly longer patient survival (4.7 ± 0.3 years) than palliative therapy concepts (1.8 ± 0.5 years, p = .0001). Patients with cervical CUP showed a significantly longer survival (4.3 ± 0.3 years) than patients with extracervical CUP (3.5 ± 0.5 years, p = .01). The identification of the primary did not significantly affect survival. CONCLUSION: This registry study confirms previous studies reporting that PET/CT significantly influences clinical management in patients with CUP, helping physicians to select a more individualized treatment and to avoid additional diagnostics. Furthermore, we could confirm that tumor localization and extent as shown by PET/CT have a significant impact on patient prognosis. KEY POINTS: • PET/CT significantly influences intended clinical management in patients with CUP, helping physicians to select a more individualized treatment and to avoid additional diagnostics. • Tumor localization and extent as shown by PET/CT have a significant impact on patient prognosis. • The identification of the primary tumor has no significant impact on overall patient survival.

Comprehensive anatomical and functional imaging in patients with type I neurofibromatosis using simultaneous FDG-PET/MRI.

PURPOSE: To demonstrate the clinical use of FDG-PET/MRI for monitoring enlargement and metabolism of plexiform neurofibromas (PNF) in patients with neurofibromatosis type 1 (NF1), in whom the development of a malignant peripheral nerve sheath tumor (MPNST) is often a life limiting event. METHODS: NF1 patients who underwent a simultaneous FDG-PET/MRI examination in our institution from September 2012 to February 2018 were included. Indication was suspicion of malignant transformation of a PNF to MPNST. A maximum of six peripheral nerve lesions per patient were defined as targets. Standardized uptake values (SUV) and apparent diffusion coefficients (ADC) were measured. The presence of target sign and contrast-medium enhancement was visually recorded. Growth rates were estimated comparing prior or follow-up examinations and correlated with FDG uptake and ADC values. The presence of CNS lesions in cerebral T2 weighted images was recorded. RESULTS: In 28 NF1 patients a total number of 83 peripheral nerve tumors, 75 benign PNFs and eight MPNSTs, were selected as target lesions. The SUVs of MPNSTs were significantly higher than the SUVs of PNF (3.84 ± 3.98 [SUVmean MPNSTs] vs. 1.85 ± 1.03 [SUVmean PNF], P < .01). Similarly, lesion SUVmean-to-liver SUVmean ratios significantly differed between MPNSTs and PNF (3.20 ± 2.70 [MPNSTs] vs. 1.23 ± 0.61 [PNF]; P < .01). For differentiation between still benign PNF and MPNSTs, we defined SUVmax ≥ 2.78 as a significant cut-off value. Growth rate of PNF correlated significantly positively with SUVmean (rs = .41; P = .003). MRI parameters like ADCmean (1.87 ± 0.24 × 10-3 mm2/s [PNF] vs. 1.76 ± 0.11 × 10-3 mm2/s [MPNSTs]; P > .05], contrast medium enhancement (P = .50) and target sign (P = .86) did not differ between groups. CONCLUSION: Simultaneous FDG-PET/MRI is a comprehensive imaging modality for monitoring PNF in NF1 patients. The combined acquisition of both morphologic information in MRI and metabolic information in PET enables the correlation of lesion growth rates with metabolic activity and to define SUV thresholds of significance to identify malignant transformation, which is of utmost clinical significance.

Diagnosis of diffuse spleen involvement in haematological malignancies using a spleen-to-liver attenuation ratio on contrast-enhanced CT images.

OBJECTIVES: We aimed to test the hypothesis that the spleen-to-liver-attenuation ratio on portal-venous enhancement phase CT images can identify diffuse splenic infiltration in subjects with lymphoma. METHODS: A database search yielded 70 subjects with malignant haematological diseases who underwent contrast-enhanced CT (CECT) between December 2010 and March 2018. Additionally, consecutive control subjects were evaluated. We compared the splenic volume, splenic attenuation, spleen-to-liver, spleen-to-aorta and spleen-to-musculature ratios on portal-venous phase CECT images, pre- to post-treatment and between the different lymphoma entities. The standard of reference for splenic involvement was normalisation of the spleen volume following chemotherapy or normalisation of FDG-uptake. RESULTS: In subjects with diffuse splenic involvement, the spleen attenuation was significantly lower before treatment (93.48 HU) compared to controls (112.39 HU; p < .01) and after successful treatment (113.39 HU; p < .01). The spleen-to-liver attenuation ratio significantly increased after treatment (p < .001) and proved significantly lower at baseline when compared to control subjects (p < .01). The spleen volume significantly decreased after successful treatment (from 586.14.87 cm3 to 284.90 cm3; p < .001). Spleen-to-liver ratio significantly increased in lymphoma patients after therapy, inversely correlating with the decline in FDG-uptake (n=10) even in patients with normal-sized spleens (2/10), staying unchanged at follow-up. The outcome variables were not significantly different between the lymphoma subtypes. CONCLUSIONS: We suggest the additional use of spleen-to-liver attenuation ratio to splenic volume alone for detection of diffuse splenic infiltration in subjects with lymphoma. The course of spleen-to-liver attenuation ratio inversely correlated with that of FDG-uptake in a subgroup of patients working accurately in normal-sized diffusely involved spleens. KEY POINTS: • Involvement of the spleen is frequent in haematological malignancies and is important for staging and appropriate treatment. • Diffuse splenic infiltration often results in only homogeneous splenomegaly without a focal lesion, but even no or only minimal increase in splenic volume is possible. In these cases diagnosis of spleen involvement is a challenge for the radiologist. • Our data support the use of the spleen-to-liver attenuation ratio in addition to size measurements for the detection of diffuse splenic infiltration in subjects with lymphoma.

Preoperative Assessment of Medication-Related Osteonecrosis of the Jaw Using [18F]fluoride Positron Emission Tomography (PET)/CT and [18F]fluorodeoxyglucose PET/MRI in Correlation with Histomorphometry and Micro-CT-A Prospective Comparative Study.

OBJECTIVES: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. METHODS: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis. RESULTS: CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas. CONCLUSIONS: In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake.

How [18F]FDG-PET/CT Affects the Management of Patients with Differentiated Thyroid Carcinoma in Clinical Routines.

PURPOSE: To investigate the impact of [18F]FDG-PET/CT on the management of differentiated thyroid carcinoma (DTC) in routine clinical settings. MATERIAL AND METHODS: In total, 98 patients (55 females, age 56 ± 18 years) with histologically confirmed thyroid cancer, including all types of DTC and poorly differentiated thyroid cancer (PDTC, n = 7), underwent [18F]FDG-PET/CT for staging or recurrence diagnostics performed using a state-of-the art clinical scanner (Biograph mCT, Siemens Healthineers) with a standardized examination protocol. The impact of PET/CT on clinical decision making was prospectively evaluated using standardized questionnaires completed by the referring physicians before and after PET/CT. Patient outcome was analyzed for OS drawn from patient records. RESULTS: Referring physicians were unable to establish a treatment plan for 81% of patients with thyroid cancer in the absence of PET/CT. The use of PET/CT had a notable influence on patient management, leading to the development of a well-defined treatment plan for 92% of patients. Moreover, after PET/CT a change in pre-PET/CT-intended treatments occurred in 32% of cases, and further invasive diagnostic could be waived in 7% of cases. [18F]FDG-PET/CT revealed a tumor detection rate of 68% (local tumor: 19%, lymph node metastases: 40%, distant metastases: 42%). HTg levels, when stimulated via TSH, were considerably higher in patients with metastases detected on PET/CT, compared to those without metastatic findings (p = 0.02). OS was significantly worse in patients with PDTC (p = 0.002) compared to follicular thyroid cancer (FTC) and PTC or even in patients with distant metastases at first diagnosis (p = 0.03). CONCLUSIONS: This prospective registry study confirms that [18F]FDG-PET/CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer by initiating treatments and reducing the uses of additional imaging and invasive tests.

How [18F]-FDG-PET/CT Affects Clinical Management of Patients with Germ Cell Tumors in the Real World.

OBJECTIVE: The aim of this study was to evaluate the impact of PET/CT on clinical management of patients with germ cell tumors (GCTs) conducted in a real-world setting, including avoidance of invasive procedures, additional diagnostic imaging, and changes in treatment. METHODS: Patients with GCTs were prospectively enrolled into a PET/CT registry study between May 2013 and April 2021. Intended patient management prior and after PET/CT was documented using standardized questionnaires. Changes in oncologic staging and clinical management after PET/CT were recorded, including planned treatment and planned additional diagnostics. RESULTS: Forty-three male patients with GCTs were included consecutively in this study. After PET/CT, oncologic staging changed in 22/43 patients (51%), with upstaging in seven cases (16%), downstaging in ten cases (23%), and cancer relapse in five cases (11%). The number of patients with intended curative treatment remained stable, while a considerable change in intended therapeutic intervention was noted after PET/CT, with an increase in planned chemotherapy from three to eleven patients and a decrease in planned surgical resection from eleven to two patients. In addition, PET/CT contributed to preventing patients from intended invasive procedures including biopsy and surgery in 8/43 (19%) cases and from additional diagnostic procedures in 25 (58%) cases. CONCLUSION: With the use of FDG-PET/CT as a tool to guide patient management in GCTs, we observed a notable impact on clinical staging and a consequent reduction in the need for additional invasive and diagnostic procedures. These findings are expected to be even more consequential in the future as treatment modalities improve and the life expectancy of GCT patients further increases. KEY POINTS: PET/CT considerably influences the clinical stage of GCT patients. PET/CT has remarkable influence on the choice of therapeutic interventions and reduces additional diagnostic procedures.

Whole-Body Magnetic Resonance Imaging (MRI) for Staging Melanoma Patients in Direct Comparison to Computed Tomography (CT): Results from a Prospective Positron Emission Tomography (PET)/CT and PET/MRI Study.

PURPOSE: The consideration of radiation exposure is becoming more important in metastatic melanoma due to improved prognoses. The aim of this prospective study was to investigate the diagnostic performance of whole-body (WB) magnetic resonance imaging (MRI) in comparison to computed tomography (CT) with 18F-FDG positron emission tomography (PET)/CT and 18F-PET/MRI together with a follow-up as the reference standard. METHODS: Between April 2014 and April 2018, a total of 57 patients (25 females, mean age of 64 ± 12 years) underwent WB-PET/CT and WB-PET/MRI on the same day. The CT and MRI scans were independently evaluated by two radiologists who were blinded to the patients' information. The reference standard was evaluated by two nuclear medicine specialists. The findings were categorized into different regions: lymph nodes/soft tissue (I), lungs (II), abdomen/pelvis (III), and bone (IV). A comparative analysis was conducted for all the documented findings. Inter-reader reliability was assessed using Bland-Altman procedures, and McNemar's test was utilized to determine the differences between the readers and the methods. RESULTS: Out of the 57 patients, 50 were diagnosed with metastases in two or more regions, with the majority being found in region I. The accuracies of CT and MRI did not show significant differences, except in region II where CT detected more metastases compared to MRI (0.90 vs. 0.68, p = 0.008). On the other hand, MRI had a higher detection rate in region IV compared to CT (0.89 vs. 0.61, p > 0.05). The level of agreement between the readers varied depending on the number of metastases and the specific region, with the highest agreement observed in region III and the lowest observed in region I. CONCLUSIONS: In patients with advanced melanoma, WB-MRI has the potential to serve as an alternative to CT with comparable diagnostic accuracy and confidence across most regions. The observed limited sensitivity for the detection of pulmonary lesions might be improved through dedicated lung imaging sequences.

[18F]Fluoride Positron-Emission Tomography (PET) and [18F]FDG PET for Assessment of Osteomyelitis of the Jaw in Comparison to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI): A Prospective PET/CT and PET/MRI Pilot Study.

To investigate imaging features of osteomyelitis of the jaw (OMJ) using [18F]fluoride positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG)-PET compared with computed tomography (CT) and magnetic resonance imaging (MRI) to assess extent and disease activity. Six female patients (55.3 ± 10.0 years) were enrolled for assessment of symptomatic OMJ. 4/6 patients underwent [18F]FDG-PET/MRI and [18F]fluoride-PET/CT, one patient MRI and [18F]fluoride-PET/CT and another patient only [18F]FDG-PET/MRI. Image analysis was performed by two radiologists, an oral and maxillofacial surgeon, and a nuclear medicine specialist. The extent of affected jawbone was analyzed both qualitatively and quantitatively, including the PET tracer uptake, CT-Hounsfield-Units (HU) and MRI parameters in affected and healthy jawbone. All patients had trabecular sclerosis in the affected jawbone compared to healthy jawbone (560 ± 328 HU vs. 282 ± 211 HU; p > 0.05), while 3/6 patients had cortical erosions. Bone marrow edema and gadolinium enhancement were documented in 5/6 patients. In affected jawbone, [18F]fluoride-uptake was increased in all patients compared to healthy jawbone (SUVmean 15.4 ± 4.2 vs. 2.1 ± 0.6; p < 0.05), and [18F]FDG-uptake was moderately higher (SUVmean 1.9 ± 0.7 vs. 0.7 ± 0.2; p > 0.05). The extent of regions with increased metabolic activity was less than the extent of morphologic changes in all patients. Information on jawbone metabolism and inflammation is different from morphologic changes and therefore has the potential to provide a more accurate and objective assessment of the extent and activity of OMJ.

Value of CT-Textural Features and Volume-Based PET Parameters in Comparison to Serologic Markers for Response Prediction in Patients with Diffuse Large B-Cell Lymphoma Undergoing CD19-CAR-T Cell Therapy.

The goal of this study was to investigate the value of CT-textural features and volume-based PET parameters in comparison to serologic markers for response prediction in patients with diffuse large B-cell lymphoma (DLBCL) undergoing cluster of differentiation (CD19)-chimeric antigen receptor (CAR)-T cell therapy. We retrospectively analyzed the whole-body (WB)-metabolic tumor volume (MTV), the WB-total lesion glycolysis (TLG) and first order textural features derived from 18F-FDG-PET/CT, as well as serologic parameters (C-reactive protein [CRP] and lactate dehydrogenase [LDH], leucocytes) prior and after CAR-T cell therapy in 21 patients with DLBCL (57.7 ± 14.7 year; 7 female). Interleukin 6 (IL-6) and IL-2 receptor peaks were monitored after treatment onset and compared with patient outcome judged by follow-up 18F-FDG-PET/CT. In 12/21 patients (57%), complete remission (CR) was observed, whereas 9/21 patients (43%) showed partial remission (PR). At baseline, WB-MTV and WB-TLG were lower in patients achieving CR (35 ± 38 mL and 319 ± 362) compared to patients achieving PR (88 ± 110 mL and 1487 ± 2254; p < 0.05). The "entropy" proved lower (1.81 ± 0.09) and "uniformity" higher (0.33 ± 0.02) in patients with CR compared to PR (2.08 ± 0.22 and 0.28 ± 0.47; p < 0.05). Patients achieving CR had lower levels of CRP, LDH and leucocytes at baseline compared to patients achieving PR (p < 0.05). In the entire cohort, WB-MTV and WB-TLG decreased after therapy onset (p < 0.01) becoming not measurable in the CR-group. Leucocytes and CRP significantly dropped after therapy (p < 0.01). The IL-6 and IL-2R peaks after therapy were lower in patients with CR compared to PR (p > 0.05). In conclusion, volume-based PET parameters derived from PET/CT and CT-textural features have the potential to predict therapy response in patients with DLBCL undergoing CAR-T cell therapy.

18F-Fluoride PET/CT Imaging of Medication-Related Osteonecrosis of the Jaw in Conservative Treatment-A Case Report.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect in antiresorptive treatment. Treatment of MRONJ is considered primarily conservative with oral mouth rinses and antibiotics but may demand surgery, depending on the complaints and general condition of the patient, the extent of the necrosis, and the overall prognosis with respect to the underlying disease. A 77 year old female patient with invasive ductal breast cancer and bone metastases was treated with intravenous bisphosphonate (BP) zoledronic acid. During therapy, she developed MRONJ in the mandible with severe pain. Clinical examination revealed confluent exposed bone of the lower left jaw and a fistula at the right molar region. The panoramic radiograph revealed a mandibular osseous involvement with diffuse radiopaque areas between radiolucent areas. For preoperative planning, 18F-fluoride positron emission tomography/computed tomography (PET/CT) of the jaw was performed, showing substantially increased 18F-fluoride uptake in regions 38 to 47 of the mandible with a focal gap in region 36 (area of clinically exposed bone). CT revealed medullary sclerosis and cortical thickening with confluent periosteal reaction and focal cortical erosion in the regions 37 to 42, whereas the regions 43 to 47 were only subtly sclerotic without cortical thickening. After systemic antibiotic therapy with sultamicillin following significant symptom and pain relief, 18F-fluoride PET/CT imaging was performed again after 5 months. No changes in either CT and PET were observed in regions 38 to 42, whereas the bony sclerosis was slightly increased in regions 43 to 47 with a slight reduction of 18F-fluoride uptake. 18F-fluoride PET/CT showed no significant changes assessing the extent of MRONJ prior and after systemic antibiotic therapy, providing no evidence that conservative treatment reduced the extent of the MRONJ-affected jawbone. The additional information of 18F-fluoride PET enables to identify the true extent of MRONJ which may be underestimated by CT imaging alone. Patients with MRONJ undergoing conservative treatment could benefit because additional imaging may be avoided as the pre-therapeutic 18F-fluoride PET/CT delivers all information needed for further treatment. Our findings support the recommendation of a surgical approach as long-term antibiotics cannot downsize the extent of MRONJ.

Value of 18F-PSMA-PET/MRI for Assessment of Recurring Ranula.

We report the case of a 6-year-old patient with suspected recurrence of a plunging ranula in clinical and ultrasonographic examination. Surgical resection of the left submandibular and sublingual glands had already been performed. Since persistent glandular tissue could not be excluded with certainty via MRI, we expanded diagnostics by performing a PET/MRI using a head and neck imaging protocol and the radiotracer 18F-PSMA-1007, which is physiologically expressed by salivary gland tissue. The 18F-PSMA-PET/MRI provided evidence of a cystically transformed, diminishing seroma in the left retro-/submandibular region. No 18F-PSMA expressing glandular tissue could be detected in the area of resection, excluding a relapse of a plunging ranula. As a consequence, we opted for a conservative treatment without further surgical intervention. We conclude that a simultaneous 18F-PSMA-PET/MRI is a comprehensive imaging modality, which can help to rule out persistent salivary tissue and recurring plunging ranula. It is a useful tool to facilitate the decision making of surgical interventions.

Impact of PET/CT on management of patients with esophageal cancer - results from a PET/CT registry study.

PURPOSE: To investigate the impact of positron emission tomography/computed tomography (PET/CT) on clinical management in patients with esophageal cancer and its link to overall survival (OS) in a real-world setting. METHODS: A patient cohort with advanced esophageal cancer undergoing PET/CT was prospectively enrolled in a registry study between 04/2013 and 06/2019. Intended patient management prior and after PET/CT was documented based on standardized questionnaire data. Management changes after PET/CT were recorded including major changes concerning the treatment goal (curative vs. palliative) and minor changes (therapy adjustments). OS was analyzed for subgroups with squamous cell carcinomas (SCC) or adenocarcinomas (AC) and stratified for extent of metastatic disease and treatment goals. RESULTS: 257 patients (53 female;65.5 ±â€¯10.0 yr.) were included. After PET/CT, major changes of intended therapy were observed in 34/257 patients (13.2%), from curative to palliative (8.2%), palliative to curative (1.9%) and from "not finally determined" to a curative (1.9%) or palliative (1.2%) concept. Minor changes were found in 62/257 patients (24.1%). Invasive procedures and additional imaging were intended in 70/257 (27.2%) and 94/257 (36.6%) patients before PET/CT and 20/257 (7.8%) and 8/257 (3.1%) patients after PET/CT. Curative therapy concepts based on PET/CT were associated with a longer OS (3.5 yr.[95%CI 3.1-3.8 yr.]) as compared to palliative concepts (0.9 yr.[95%CI 0.6-1.2 yr.];p < 0.0001). Patients with SCC had a worse prognosis (2.4 yr.[95%CI 2.0-2.9 yr.]) as compared to patients with AC (3.2 yr.[95%CI 2.7-3.7 yr.];p = 0.01). CONCLUSIONS: In patients with advanced esophageal cancer, PET/CT has a significant impact on clinical management by improving the selection of individualized treatment strategies and avoiding additional diagnostic procedures.

Case Report: Combined CDK4/6 and MEK Inhibition in Refractory CDKN2A and NRAS Mutant Melanoma.

There are only limited treatment options for metastatic NRAS mutant melanoma patients with resistance to immune checkpoint inhibitors. Besides activation of the mitogen-activated protein (MAP) kinase pathway, they often have additional disturbances in cell cycle regulation. However, unlike BRAF mutant melanoma, no targeted therapy has yet been approved for NRAS mutant melanoma so far. Here we present a NRAS mutant melanoma patient with response to combined binimetinib and ribociclib therapy following characterization of the molecular defects of the tumor by panel sequencing. Next generation sequencing (708 cancer genes) of a soft tissue metastasis revealed a homozygous deletion of CDKN2A in addition to the previously known NRAS mutation, as well as amplification of CCNE1 and CDK6. Immunohistochemical staining of the altered cell cycle genes confirmed loss of p16, reduced expression of p21 and high expression of CDK6 and cyclin D1. As the patient had been progressive on combined immunotherapy, targeted therapy with combined MEK and CDK4/6 inhibition was initiated as recommended by the molecular tumor board. Response to treatment was monitored with PET/CT and liquid biopsy, serum LDH, and S100. In addition, a patient-derived xenograft (PDX) was used to prove the efficacy of the two drugs in combination. Furthermore, senescence-associated beta-galactosidase staining showed that more cells were senescent under the combination treatment of binimetinib and ribociclib. Our case demonstrates how an individualized, molecular-based therapeutic approach could be found based on next-generation sequencing results. Furthermore our report highlights the fruitful and efficient collaboration of dermatooncologists, human geneticists, molecular pathologists, biochemists, radiologists, and nuclear physicians. Further studies are urgently needed to expand the very limited therapeutic landscape of NRAS mutated melanoma.

Mid-term response assessment in multiple myeloma using a texture analysis approach on dual energy-CT-derived bone marrow images - A proof of principle study.

PURPOSE: To identify textural features on dual-energy CT (DECT)-generated virtual non calcium (VNC) bone marrow images in a small group of patients with multiple myeloma undergoing systemic treatment which could potentially help for mid-term response assessment. METHODS: 44 patients (59.1 ±â€¯11.2 yr.) with multiple myeloma who underwent unenhanced whole-body reduced-dose DECT before and after systemic therapy were evaluated. All patients had current hematologic laboratory tests including serum levels of immunoglobulins, albumin, and total proteins. Using DECT post-processing, bone marrow images of the axial skeleton were reconstructed. The vertebral bodies T10-L5 were segmented for quantification of 1st order (n = 18) and 2nd order Gray Level Co-occurrence Matrix (GLCM) textural features (n = 23) based on an open-source radiomics library (Pyradiomics), which were then compared with the hematologic response category to treatment. Five patients underwent only active surveillance at intervals after previous successful therapy. RESULTS: According to hematologic diagnosis, 29 patients were classified as complete response (CR), 10 as partial response (PR) and 5 as stable disease (SD). We observed a significant drop of the 1st order textural features "10th percentile" (p = 0.009), "median" (p = 0.01), and "minimum" (p < 0.0001) after treatment, whereas the 1st order feature "range" (p = 0.0004) and the 2nd order GLCM feature "difference variance" (p = 0.007) significantly increased in patients experiencing CR. A similar trend, however, without statistical significance, could be observed in patients achieving PR after treatment. 2nd order GLCM feature "difference variance" proved to be a significant discriminator (p = 0.01) between patients with CR and PR (sensitivity 0.93, specificity 0.70) for a cut-off value of -0.28. In patients classified CR, both the mean serum protein and the beta-2 microglobulin decreased after treatment, whereas the serum albumin increased (p < 0.01). The same trend without significance could be observed in patients classified PR. CONCLUSIONS: Changes in textural features applied on VNC bone marrow images in the pre- and posttreatment settings correlate well with myeloma-specific hematologic parameters and provide complementary information for the assessment of the late effects of treatment on the bone marrow.

Complementary role of computed tomography texture analysis for differentiation of pancreatic ductal adenocarcinoma from pancreatic neuroendocrine tumors in the portal-venous enhancement phase.

PURPOSE: To assess the role of CT-texture analysis (CTTA) for differentiation of pancreatic ductal adenocarcinoma (PDAC) from pancreatic neuroendocrine neoplasm (PNEN) in the portal-venous phase as compared with visual assessment and tumor-to-pancreas attenuation ratios. METHODS: 53 patients (66.1 ± 8.6y) with PDAC and 42 patients (65.5 ± 12.2y) with PNEN who underwent contrast-enhanced CT for primary staging were evaluated. Volumes of interests (VOIs) were set in the tumor tissue at the portal-venous phase excluding adjacent structures. Based on pyradiomics library, 92 textural features were extracted including 1st, 2nd, and higher order features, and then compared between PNEN and PDAC. The visual assessment classified tumors into hypo-, iso-, or hyperdense to pancreas parenchyma or into homogeneous/heterogeneous. Additionally, attenuation ratios between the tumors and the non-involved pancreas were calculated. RESULTS: 8/92 (8.6%) highly significant (p < 0.005) discriminatory textural features between PDAC and PNEN were identified including the 1st order features "median," "total energy," "energy," "10th percentile," "90th percentile," "minimum," "maximum," and the 2nd order feature "Gray-Level co-occurrence Matrix (GLCM) Informational Measure of Correlation (Imc2)." In PNEN, the higher order feature "GLSZM Small Area High Gray-Level Emphasis" proved significantly higher in G1 compared to G2/3 tumors (p < 0.05). The tumor/parenchyma ratios as well as the visual assessment into hypo-/iso-/hyperdense or homogeneous/heterogeneous did not significantly differ between PDAC and PNEN. CONCLUSIONS: Our data indicate that CTTA is a feasible tool for differentiation of PNEN from PDAC and also of G1 from G2/3 PNEN in the portal-venous phase. Visual assessment and tumor-to-parenchyma ratios were not useful for discrimination.

Computed tomography texture analysis for assessment of chemotherapy response of Hodgkin lymphoma.

The aim of this study was to test the hypothesis that computed tomography texture analysis (CTTA) is accurate for response assessment of Hodgkin lymphoma (HL).A total of 100 patients with HL were identified. CTTA in baseline and interim staging was performed generating volume of interests in lymphoma tissue from which CTTA features including 1st, 2nd, and higher order textural features were extracted. Baseline and interim 2-deoxy-fluor-glucose positron emission tomography results were used to determine therapy response and compared to CTTA in terms of patient outcome.At interim, 1st-order features yielded a significant drop (e.g., entropy of heterogeneity, P = .01) or a significant rise (deviation, P < .001), whereas 2nd and higher order features decreased (e.g., entropy of co-occurrence matrix, P < .001). Patients achieving complete remission at end of treatment had a significantly lower entropy of heterogeneity at baseline and interim compared to patients achieving partial remission (P < .05).CT textural features change in parallel to metabolic therapy response, and are therefore a feasible diagnostic tool for a more accurate response assessment of HL.

Clinical and prognostic value of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT: a comparison with serologic markers of tumor burden and inflammation.

BACKGROUND: To investigate the association of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT with serologic tumor markers and inflammatory markers and the role as imaging predictors for overall survival. METHODS: A patient cohort with advanced melanoma undergoing 18F-FDG-PET/CT for planning metastasectomy between 04/2013 and 01/2015 was retrospectively included. The volumetric PET parameters whole-body MTV and whole-body TLG as well as the standard uptake value (SUV) peak were quantified using 50%-isocontour volumes of interests (VOIs) and then correlated with the serologic parameters lactate dehydrogenase (LDH), S-100 protein, c-reactive protein (CRP) and alkaline phosphatase (AP). PET parameters were dichotomized by their respective medians and correlated with overall survival (OS) after PET/CT. OS was compared between patients with or without metastases and increased or not-increased serologic parameters. RESULTS: One hundred seven patients (52 female; 65 ± 13.1yr.) were included. LDH was strongly associated with MTV (rP = 0.73, p <  0.001) and TLG (rP = 0.62, p <  0.001), and moderately associated with SUVpeak (rP = 0.55, p <  0.001). S-100 protein showed a moderate association with MTV (rP = 0.54, p <  0.001) and TLG (rP = 0.48, p <  0.001) and a weak association with SUVpeak (rP = 0.42, p <  0.001). A strong association was observed between CRP and MTV (rP = 0.66, p <  0.001) and a moderate to weak association between CRP and TLG (rP = 0.53, p <  0.001) and CRP and SUVpeak (rP = 0.45, p <  0.001). For differentiation between patients with or without metastases, receiver operating characteristic (ROC) analysis revealed a cut-off value of 198 U/l for serum LDH (AUC 0.81, sensitivity 0.80, specificity 0.72). Multivariate analysis for OS revealed that both MTV and TLG were strong independent prognostic factors. TLG, MTV and SUVpeak above patient median were accompanied with significantly reduced estimated OS compared to the PET parameters below patient median (e.g. TLG: 37.1 ± 3.2 months vs. 55.9 ± 2.5 months, p <  0.001). Correspondingly, both elevated serum LDH and S-100 protein were accompanied with significantly reduced OS (36.5 ± 4.9 months and 37.9 ± 4.4 months) compared to normal serum LDH (49.2 ± 2.4 months, p = 0.01) and normal S-100 protein (49.0 ± 2.5 months, p = 0.01). CONCLUSIONS: Tumor volumetric parameters in 18F-FDG-PET/CT serve as prognostic imaging biomarkers in patients with advanced melanoma which are associated with established serologic tumor markers and inflammatory markers.