Diagnosis of sarcopenia on thoracic computed tomography and its association with postoperative survival after anatomic lung cancer resection.

Computer tomography-derived skeletal muscle index normalized for height in conjunction with muscle density enables single modality-based sarcopenia assessment that accounts for all diagnostic criteria and cutoff recommendations as per the widely accepted European consensus. Yet, the standard approach to quantify skeletal musculature at the third lumbar vertebra is limited for certain patient groups, such as lung cancer patients who receive chest CT for tumor staging that does not encompass this lumbar level. As an alternative, this retrospective study assessed sarcopenia in lung cancer patients treated with curative intent at the tenth thoracic vertebral level using appropriate cutoffs. We showed that skeletal muscle index and radiation attenuation at level T10 correlate well with those at level L3 (Pearson's R = 0.82 and 0.66, p < 0.001). During a median follow-up period of 55.7 months, sarcopenia was independently associated with worse overall (hazard ratio (HR) = 2.11, 95%-confidence interval (95%-CI) = 1.38-3.23, p < 0.001) and cancer-specific survival (HR = 2.00, 95%-CI = 1.19-3.36, p = 0.009) of lung cancer patients following anatomic resection. This study highlights feasibility to diagnose sarcopenia solely by thoracic CT in accordance with the European consensus recommendations. The straightforward methodology offers easy translation into routine clinical care and potential to improve preoperative risk stratification of lung cancer patients scheduled for surgery.

Head-to-Head Comparison of Dual-Source and Split-Beam Filter Multi-Energy CT versus SPECT/CT for Assessing Lobar Lung Perfusion in Emphysema.

Purpose: To evaluate dual-source and split-beam filter multi-energy chest CT in assessing pulmonary perfusion on a lobar level in patients with lung emphysema, using perfusion SPECT as the reference standard. Materials and Methods: Patients with emphysema evaluated for lung volume reduction therapy between May 2016 and February 2021 were retrospectively included. All patients underwent SPECT and either dual-source or split-beam filter (SBF) multi-energy CT. To calculate the fractional lobar lung perfusion (FLLP), SPECT acquisitions were co-registered with chest CT scans (hereafter, SPECT/CT) and semi-manually segmented. For multi-energy CT scans, lung lobes were automatically segmented using a U-Net model. Segmentations were manually verified. The FLLP was derived from iodine maps computed from the multi-energy data. Statistical analysis included Pearson and intraclass correlation coefficients and Bland-Altman analysis. Results: Fifty-nine patients (30 male, 29 female; 31 underwent dual-source CT, 28 underwent SBF CT; mean age for all patients, 67 years ± 8 [SD]) were included. Both multi-energy methods significantly correlated with the SPECT/CT acquisitions for all individual lobes (P < .001). Pearson correlation concerning all lobes combined was significantly better for dual-source (r = 0.88) than for SBF multi-energy CT (r = 0.78; P = .006). On the level of single lobes, Pearson correlation coefficient differed for the right upper lobe only (dual-source CT, r = 0.88; SBF CT, r = 0.58; P = .008). Conclusion: Dual-source and SBF multi-energy CT accurately assessed lung perfusion on a lobar level in patients with emphysema compared with SPECT/CT. The overall correlation was higher for dual-source multi-energy CT.Keywords: Chronic Obstructive Pulmonary Disease, Comparative Studies, Computer Applications, CT Spectral Imaging, Image Postprocessing, Lung, Pulmonary Perfusion© RSNA, 2023.

18F-FDG PET/CT-derived total lesion glycolysis predicts abscess formation in patients with surgically confirmed infective endocarditis: Results of a retrospective study at a tertiary center.

BACKGROUND: Abnormal activity of 18F-FDG PET/CT is a major Duke criterion in the diagnostic work-up of infective prosthetic valve endocarditis (IE). We hypothesized that quantitative lesion assessment by 18F-FDG PET/CT-derived standard maximum uptake ratio (SURmax), metabolic volume (MV), and total lesion glycolysis (TLG) might be useful in distinct subgroups of IE patients (e.g. IE-related abscess formation). METHODS: All patients (n = 27) hospitalized in our tertiary IE referral medical center from January 2014 to October 2018 with preoperatively performed 18F-FDG PET/CT and surgically confirmed IE were included into this retrospective analysis. RESULTS: Patients with surgically confirmed abscess formation (n = 10) had significantly increased MV (by ~ fivefold) and TLG (by ~ sevenfold) as compared to patients without abscess (n = 17). Receiver operation characteristics (ROC) analyses demonstrated that TLG (calculated as MV × SURmean, i.e. TLG (SUR)) had the most favorable area under the ROC curve (0.841 [CI 0.659 to 1.000]) in predicting IE-related abscess formation. This resulted in a sensitivity of 80% and a specificity of 88% at a cut-off value of 14.14 mL for TLG (SUR). CONCLUSION: We suggest that 18F-FDG PET/CT-derived quantitative assessment of TLG (SUR) may provide a novel diagnostic tool in predicting endocarditis-associated abscess formation.

Diagnostic value of FDG PET/CT imaging in patients with surgically managed infective endocarditis: results of a retrospective analysis at a tertiary center.

BACKGROUND: We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE). METHODS: We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT. RESULTS: Final analysis included 29 patients, whereof 28 patients had surgically proven IE. FDG PET/CT scan was true-positive in 15 patients (sensitivity (SEN) 56%) and false-negative in 12 patients. Combination of Duke criteria (DC) with FDG PET/CT scan resulted in gain of SEN for all patients with confirmed IE (SEN of DC 79% vs SEN of combination DC and FDG PET/CT 89%), driven by a relevant gain in PVE patients only (SEN of DC 78% vs SEN of combination DC and FDG PET/CT 94%). Interestingly, higher prosthesis age was observed in patients with false-negative scans. CONCLUSIONS: We found a SEN of 56% for FDG PET/CT in a real-world cohort of patients with surgically proven IE which was associated with a 16% gain of IE diagnosis in patients with PVE when combined with DC.

Dose estimates of occupational radiation exposure during radioguided surgery of Tc-99m-PSMA-labeled lymph nodes in recurrent prostate cancer.

AIM: [99mTc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99mTc- activity below the exemption limit of 10 MBq at the time of surgery. Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations. METHODS: In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p. i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of 99mTc-PSMA-I&S in patients was determined from repeated dose rate measurements to estimate dose parameters of relevance for radiation protection. External exposures of the surgeons were measured with personal dosimeters calibrated in Hp(10). The surgeon's finger dose Hp(0.07) is estimated from radioactivity measured in resected lymph nodes. Potenzial incorporations were estimated for an activity of 10 MBq. RESULTS: From the first 6 subsequent patients, an effective half-life of 4.15 h was observed. Assuming an operation time 24 h p. i., the OAR was 550 MBq. Operations lasting in average 2 h in a distance of 0.25 m to the patient imply a body dose for surgeons of 4.16 µSv per procedure. Based on these estimates, the surgeon's Hp(10) is less than 1 mSv per year with up to 241 operations per year. Hp(0.07) and potential incorporation of activity do not lead to further limitations. SUMMARY: All radiation protection regulations are met with adherence to OAR recommended here without triggering the full monitoring obligations from radiation protection regulations.

Head and neck melanoma: outcome and predictors in a population-based cohort study.

BACKGROUND: To evaluate predictive clinico-pathological characteristics on outcome in head and neck melanoma (HNM) in a population-based study with particular emphasis on the prognostic effect of sentinel lymph node biopsy (SLNB), Charlson comorbidity index (CCI) and distinct tumor localisations. METHODS: Here we primarily describe a retrospective multicenter population-based cohort study with 402 patients having undergone resection with curative intent of HNM between 2010 and 2017. SLNB was used in the diagnosis of 79 HNM patients. Outcome was analyzed, focusing on SLNB, CCI as well as tumor localisation. Overall survival (OAS) und recurrence free survival (RFS) was examined by uni- and multivariate analysis. RESULTS: Histopathologically verified lymph node metastasis according to SLNB was associated with impaired RFS in HNM patients (p = 0.004). Especially in higher tumor stages, the sole implementation of SLNB improved survival significantly in the present cohort (p = 0.042). With most of the HNM being located in the face, melanoma of the scalp and neck could be linked to deteriorated patient's outcome in uni- as well as multivariate analysis (p = 0.021, p = 0.004). CONCLUSIONS: SLNB is a useful tool in predicting development of distant metastasis after HNM resection with curative intent. Especially in higher tumor stages, performing a SLNB ameliorated survival of HNM patients. Additionally, CCI as well as a distinct tumor localisations in HNM were identified as important risk factors in our population-based cohort study.

Complementary imaging of ultrasound and PET/CT: A new opportunity?

AIM: To evaluate the effectiveness of complementary imaging of high-resolution ultrasound including CEUS with PET/CT for tissue characterization and tumor detection. MATERIAL AND METHODS: 100 patients were examined with PET/CT and US/CEUS between January 2018 until February 2020. All patients underwent PET/CT followed by selective US/CEUS within 4 weeks. Comparison regarding concordant or diverging findings in PET/CT and US. Analysis of the differences concerning the lesions number of found by PET/CT and US/CEUS or the possibility of a secured diagnosis following ultrasound causing therapeutic changes. RESULTS: Diverging findings regarding the number of liver lesions in PET/CT and CEUS were found in 35 out of 64 patients (54%). Regarding renal lesions, a more definite diagnosis following ultrasound, causing a change of therapeutic approach, was achieved in 89%. Concordant results in PET/CT and US were found in 83% of patients with splenic and nodal findings. In 78% of patients with increased musculoskeletal or soft tissue tracer uptake, US was able to make a secured diagnosis with therapeutic changes. CONCLUSION: The present results indicate a strong benefit of complementary imaging of PET/CT and selective, high-resolution ultrasound especially in patients with liver, renal and musculoskeletal or soft tissue findings.

Identification and In-Depth Analysis of the Novel FGFR2-NDC80 Fusion in a Cholangiocarcinoma Patient: Implication for Therapy.

Fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a new therapeutic target for cholangiocarcinoma in clinical practice following the United States Food and Drug Administration (FDA) approval of Pemigatinib in May 2020. FGFR2 fusions can result in a ligand-independent constitutive activation of FGFR2 signaling with a downstream activation of multiple pathways, including the mitogen-activated protein (MAPK) cascade. Until today, only a limited number of fusion partners have been reported, of which the most prevalent is BicC Family RNA Binding Protein (BICC1), representing one-third of all detected FGFR2 fusions. Nonetheless, in the majority of cases rare or yet unreported fusion partners are discovered in next-generation sequencing panels, which confronts clinicians with a challenging decision: Should a therapy be based on these variants or should the course of treatment follow the (limited) standard regime? Here, we present the case of a metastasized intrahepatic cholangiocarcinoma harboring a novel FGFR2-NDC80 fusion, which was discussed in our molecular tumor board. The protein NDC80 kinetochore complex component (NDC80) is an integral part of the outer kinetochore, which is involved in microtubule binding and spindle assembly. For additional therapeutic guidance, an immunohistochemical analysis of the predicted fusion and downstream effector proteins was performed and compared to cholangiocarcinoma samples of a tissue microarray. The FGFR2-NDC80 fusion resulted in strong activation of the FGFR2 signaling pathway. These supporting results led to a treatment recommendation of Pemigatinib. Unfortunately, the patient passed away before the commencement of therapy.

FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). METHODS: Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. RESULTS: Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32-45%) and 84% (CI: 78-88%), specificity 100% (CI: 99-100%) and 100% (CI: 99-100%), positive predictive value 100% (CI: 96-100%) and 100% (CI: 98-100%), and negative predictive value 84% (CI: 81-86%) and 95% (CI: 93-97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. CONCLUSION: In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. TRIAL REGISTRATION: NCT00554164 and NCT01478542.

Successful auxiliary two-staged partial resection liver transplantation (ASPIRE-LTx) for end-stage liver disease to avoid small-for-size situations.

BACKGROUND: Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. CASE PRESENTATION: Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. CONCLUSIONS: Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety.

Total lesion glycolysis in oral squamous cell carcinoma as a biomarker derived from pre-operative FDG PET/CT outperforms established prognostic factors in a newly developed multivariate prediction model.

PURPOSE: Retrospective study to investigate the impact of image derived biomarkers from [18F]FDG PET/CT prior to surgical resection in patients with initial diagnosis of oral squamous cell carcinoma (OSCC), namely SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor to predict overall survival (OS). MATERIALS AND METHODS: 127 subsequent patients with biopsy-proven OSCC were included who underwent [18F]FDG PET/CT before surgery. SUVmax, SUVmean, MTV and TLG of the primary tumor were measured. OS was estimated according to Kaplan-Meier and compared between median-splitted groups by the log-rank test. Prognostic parameters were analyzed by uni-/multivariate Cox-regression. RESULTS: During follow-up 52 (41%) of the patients died. Median OS was longer for patients with lower MTV or lower TLG. SUVmax and SUVmean failed to be significant predictors for OS. Univariate Cox-regression identified MTV, TLG, lymph node status and UICC stage as prognostic factors. By multivariate Cox-regression MTV and TLG turned out to be independent prognostic factors for OS. CONCLUSIONS: The pre-therapeutic [18F]FDG PET/CT parameters MTV and TLG in the primary tumor are prognostic for OS of patients with an initial diagnosis of OSCC. TLG is the strongest independent prognostic factor for OS and outperforms established prognostic parameters in OSCC.

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.

PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

Non-Invasive Prediction of IDH Mutation in Patients with Glioma WHO II/III/IV Based on F-18-FET PET-Guided In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning.

Isocitrate dehydrogenase (IDH)-1 mutation is an important prognostic factor and a potential therapeutic target in glioma. Immunohistological and molecular diagnosis of IDH mutation status is invasive. To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, directly in vivo. However, these methods are technically challenging and not broadly available. Therefore, we explored the use of machine learning for the non-invasive, inexpensive and fast diagnosis of IDH status in standard 1H-magnetic resonance spectroscopy (1H-MRS). To this end, 30 of 34 consecutive patients with known or suspected glioma WHO grade II-IV were subjected to metabolic positron emission tomography (PET) imaging with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) for optimized voxel placement in 1H-MRS. Routine 1H-magnetic resonance (1H-MR) spectra of tumor and contralateral healthy brain regions were acquired on a 3 Tesla magnetic resonance (3T-MR) scanner, prior to surgical tumor resection and molecular analysis of IDH status. Since 2-HG spectral signals were too overlapped for reliable discrimination of IDH mutated (IDHmut) and IDH wild-type (IDHwt) glioma, we used a nested cross-validation approach, whereby we trained a linear support vector machine (SVM) on the complete spectral information of the 1H-MRS data to predict IDH status. Using this approach, we predicted IDH status with an accuracy of 88.2%, a sensitivity of 95.5% (95% CI, 77.2-99.9%) and a specificity of 75.0% (95% CI, 42.9-94.5%), respectively. The area under the curve (AUC) amounted to 0.83. Subsequent ex vivo 1H-nuclear magnetic resonance (1H-NMR) measurements performed on metabolite extracts of resected tumor material (eight specimens) revealed myo-inositol (M-ins) and glycine (Gly) to be the major discriminators of IDH status. We conclude that our approach allows a reliable, non-invasive, fast and cost-effective prediction of IDH status in a standard clinical setting.

Candida Endocarditis in Patients with Candidemia: A Single-Center Experience of 14 Cases.

A retrospective, single-center analysis of 14 cases of Candida endocarditis (from 355 candidemia cases during the years 2012-2019) revealed a high in-hospital mortality (57.1%), a high proportion of healthcare-associated infections (13/14) and a high treatment preference for echinocandins. Transthoracic echocardiography and 18F-FDG PET/CT had a sensitivity of 54.5% and 57.1%, respectively. Patients were older than previously described and most patients with Candida endocarditis had persistent candidemia for ≥ 3 days despite antifungal therapy.

FDG-PET Imaging for Hodgkin and Diffuse Large B-Cell Lymphoma-An Updated Overview.

Since the mid-1990s, 18F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future.

[PET/CT and PET/MRI in Head and Neck Cancer]. / PET/CT und PET/MRT bei Tumoren des Kopf-Hals-Bereichs.

Positron emission tomography (PET) with 18F-fluordeoxyglucose (FDG) in combination with computed tomography (CT) is well established for the diagnostic work-up of patients with head and neck cancer. Possible applications include the detection of an occult primary tumor metastatic to cervical nodes, locoregional staging, assessment of treatment response to external beam irradiation (also in combination with chemotherapy), and surveillance for recurrence. The success of high-precision irradiation techniques such as intensity-modulated radiation therapy (IMRT) appears to be improved by delineating the tumor volume using PET/CT. Combined PET/Magnetic Resonance Imaging (MRI) offers advantages in staging with regard to increased anatomical details and radiation dose reduction but is inferior to PET/CT in the detection of pulmonary metastases and secondary tumors. As shown by a randomized trial in patients with advanced head and neck cancer, neck dissection can be omitted if FDG PET/CT is negative after radiochemotherapy and survival is not compromised. With this high level of evidence PET/CT in head and neck cancer currently found its way into the catalog of diagnostic procedures for patients in the statutory health insurances.

In vivo confirmation of altered hepatic glucose metabolism in patients with liver fibrosis/cirrhosis by 18F-FDG PET/CT.

OBJECTIVE: The aim of this study was to assess the value of 18F-FDG PET/CT for quantitative assessment of hepatic metabolism in patients with different stages of liver fibrosis/cirrhosis. MATERIALS AND METHODS: 18F-FDG PET/CT scans of 37 patients either with or without liver fibrosis/cirrhosis, classified according to the METAVIR score (F0-F4) obtained from histopathological analysis of liver specimen, were analyzed retrospectively and classified as follows: no liver fibrosis (F0, n = 6), mild liver fibrosis (F1, n = 11), advanced liver fibrosis (F2, n = 6), severe liver fibrosis (F3, n = 5), and liver cirrhosis (F4, n = 11). The liver-to-blood ratio (LBR, scan time corrected for a reference time of 75 min) was compared between patient groups. RESULTS: Patients with liver fibrosis or cirrhosis (≥ F1; LBR 1.53 ± 0.35) showed a significant higher LBR than patients with normal liver parenchyma (F0, 1.08 ± 0.23; P = 0.004). In direct comparison, LBR increased up to the advanced stage of liver fibrosis (F2; 2.00 ± 0.40) and decreased until liver cirrhosis is reached (F4, 1.32 ± 0.14). CONCLUSION: Functional changes in liver parenchyma during liver fibrosis/cirrhosis affect hepatic glucose metabolism and significantly differ between stages of liver fibrosis/cirrhosis, classified according to the METAVIR scoring system, as demonstrated by LBR quantification by 18F-FDG PET/CT.

Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension.

Medullary thyroid cancer (MTC) is a rare malignancy with a poor prognosis. First line therapy is surgery, which is the only curative method of the disease. However, in non-operable cases or with tumor progression and metastases, a systemic treatment is necessary. This form of cancer is often insensitive to conventional chemotherapy, but the use of tyrosine kinase inhibitors (TKIs), such as pazopanib, cabozantinib, and vandetanib, has shown promising results with an increase in progression-free survival and prolonged lifetime. Therefore, we focused on the pharmacological characteristics of TKIs, their mechanism of action, their application as a secondary treatment option for MTC, their efficacy as a cancer drug treatment, and reviewed the ongoing clinical trials. TKIs also act systemically causing various adverse events (AEs). One common AE of this treatment is hypertension, known to be associated with cardiovascular disease and can therefore potentially worsen the well-being of the treated patients. The available treatment strategies of drug-induced hypertension were discussed. The mechanism behind the development of hypertension is still unclear. Therefore, the treatment of this AE remains symptomatic. Thus, future studies are necessary to investigate the link between tumor growth inhibition and hypertension. In addition, optimized, individual treatment strategies should be implemented.

Fluorescence-guidance in non-Gadolinium enhancing, but FET-PET positive gliomas.

OBJECTIVES: We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging-MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). PATIENTS AND METHOD: Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. RESULTS: In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. DISCUSSION AND CONCLUSION: Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.

Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFRmut NSCLC in diagnosis, follow-up and treatment.

Brain and leptomeningeal metastasis (LMM) of non-small cell lung cancer is still associated with poor prognosis. Moreover, the current diagnostic standard for LMM often yields false negative results and the scientific progress in this field is still unsatisfying. We present a case of a 71-year old patient with an isolated LMM. While standard diagnostics could only diagnose a cancer of unknown primary, the use of [68Ga]-Pentixafor-PET/CT (CXCR4-PET/CT, a radiotracer targeting CXCR4) and a liquid biopsy of the cerebrospinal fluid revealed the primary NSCLC. The detection of L858R-EGFR, a common driver mutation in NSCLC, enabled us to treat the patient with Afatinib and monitor treatment using [68Ga]-Pentixafor PET/CT. To estimate the impact of CXCR4 signaling and its ligands in NSCLC brain metastasis we looked at their expression and correlation with EGFR mutations in a primary and brain metastasis data set and investigated the previously described binding of extracellular ubiquitin to CXCR4. In conclusion, we describe a novel approach to improve diagnostics towards LMM and underline the impact of the CXCL12/CXCR4 axis in brain metastasis in a subset of NSCLC patients. We cannot confirm a correlation of CXCR4 expression with EGFR mutations or the binding of extracellular ubiquitin as previously reported.