Retrospective analysis of treatment decisions and clinical outcome of Lisfranc injuries: operative vs. conservative treatment.

PURPOSE: Lisfranc injuries are rare and often pose a challenge for surgeons, particularly in initially missed or neglected cases. The evidence on which subtypes of Lisfranc injuries are suitable for conservative treatment or should undergo surgery is low. The aim of this study was to retrospectively analyze treatment decisions of Lisfranc injuries and the clinical outcome of these patients within the last ten years. METHODS: All patients treated due to a Lisfranc injury in a German level I trauma centre from January 2011 until December 2020 were included in this study. Radiologic images and medical data from the patient files were analyzed concerning the classification of injury, specific radiologic variables, such as the Buehren criteria, patient baseline characteristics, and patient outcome reported with the Foot Function Index (FFI). RESULTS: Ninety-nine patients were included in this study (conservative = 20, operative = 79). The overall clinical outcome assessed by the FFI was good (FFI sum 23.93, SD 24.93); patients that were identified as suitable for conservative treatment did not show inferior functional results. Qualitative radiological factors like the grade of displacement and the trauma mechanism were more strongly associated with the decision for surgical treatment than quantitative radiologic factors such as the distance from the first to the second metatarsal bone. CONCLUSION: If the indication for conservative or operative treatment of Lisfranc injuries is determined correctly, the clinical outcome can be comparable. These decisions should be based on several factors including quantitative and qualitative radiologic criteria, as well as the trauma mechanism.

[177Lu]Lu-PSMA Therapy as an Individual Treatment Approach for Patients with High-Grade Glioma: Dosimetry Results and Critical Statement.

The theranostic use of prostate-specific membrane antigen (PSMA) appears to be promising in patients with high-grade glioma. This study investigated [177Lu]Lu-PSMA therapy as an individual treatment approach with a focus on intratherapeutic dosimetry. Methods: Three patients were treated with a median of 6.03 GBq (interquartile range [IQR], 5.74-6.10) of [177Lu]Lu-PSMA. Intratherapeutic dosimetry was performed using a hybrid scenario with planar whole-body scintigraphy at 2, 24, and 48 h after treatment injection and SPECT/CT at 48 h after injection. Additive whole-body scintigraphy at 8 d after injection was performed on 1 patient. Results: The median doses were 0.56 Gy (IQR, 0.36-1.25 Gy) to tumor, 0.27 Gy (IQR, 0.16-0.57 Gy) to risk organs, 2.13 Gy (IQR, 1.55-2.89 Gy) to kidneys, and 0.76 Gy (IQR, 0.70-1.20 Gy) to salivary glands. Whole-body exposure was 0.11 Gy (IQR, 0.06-0.18 Gy). Conclusion: Because the intratherapeutic tumor dose is lower than that used in external radiation oncology, the effectiveness of treatment is questionable.

[68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma.

Purpose: High-grade gliomas (HGG) are still associated with a dismal prognosis. Prostate specific membrane antigen (PSMA) is discussed as a theranostic target for PSMA-directed radioligand therapy ([177Lu]Lu-PSMA RLT). Here, we report on the correlation of [68Ga]Ga-PSMA uptake with histological PSMA expression and on our preliminary experience with [177Lu]Lu-PSMA RLT in relapsing HGG. Methods: Patients with relapsing HGG underwent [68Ga]Ga-PSMA PET/MRI to evaluate eligibility for an individualized treatment approach with [177Lu]Lu-PSMA. Standard uptake values (SUV) for tumor and liver and respective tumor-to-background ratios (compared to the liver) (TBR) on [68Ga]Ga-PSMA PET/MRI were assessed. Eligibility criteria for [177Lu]Lu-PSMA therapy were exhaustion of all standard treatment options available and TBRmax>1.0. In 11 samples, immunohistochemical PSMA expression was determined, quantified using the H-score and correlated with uptake on [68Ga]Ga-PSMA PET/MRI. Results: We included 20 patients with a median age of 53 years (IQR 42-57). The median SUV on [68Ga]Ga-PSMA PET/MRI was 4.5 (3.7-6.2) for SUVmax and 1.4 (1.1-1.7) for SUVmean. The respective TBR was maximum 0.6 (0.4-0.8) and mean 0.3 (0.2-0.4). High TBRmax correlated with increased endothelial PSMA expression [H-score of 65 (62.5-77.5)]. Three patients (15%) presented a TBRmax>1.0 and qualified for [177Lu]Lu-PSMA RLT. No treatment related toxicity was observed. Conclusion: Only a minority of patients with relapsing HGG qualified for [177Lu]Lu-PSMA RLT. Our data demonstrates that PSMA expression in the neo-vasculature corresponds to PSMA uptake on [68Ga]Ga-PSMA PET/MRI and might be used as a screening tool for patient selection. Future prospective studies need to focus the debate on TBRmax thresholds as inclusion criteria for PSMA RLT.

Transarterial Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma Patients: Outcome Assessment Applying a Prognostic Score.

Radioembolization (RE) is a viable therapy option in patients with intrahepatic cholangiocarcinoma (ICC). This study delineates a prognostic score regarding overall survival (OS) after RE using routine pre-therapeutic parameters. A retrospective analysis of 39 patients (median age, 61 [range, 32−82] years; 26 females, 13 males) with ICC and 42 RE procedures was conducted. Cox regression for OS included age, ECOG, hepatic and extrahepatic tumor burden, thrombosis of the portal vein, ascites, laboratory parameters and dose reduction due to hepatopulmonary shunt. Median OS after RE was 8.0 months. Using univariable Cox, ECOG ≥ 1 (hazard ratio [HR], 3.8), AST/ALT quotient (HR, 1.86), high GGT (HR, 1.002), high CA19-9 (HR, 1.00) and dose reduction of 40% (HR, 3.8) predicted shorter OS (each p < 0.05). High albumin predicted longer OS (HR, 0.927; p = 0.045). Multivariable Cox confirmed GGT ≥ 750 [U/L] (HR, 7.84; p < 0.001), ECOG > 1 (HR, 3.76; p = 0.021), albumin ≤ 41.1 [g/L] (HR, 3.02; p = 0.006) as a three-point pre-therapeutic prognostic score. More specifically, median OS decreased from 15.3 months (0 risk factors) to 7.6 months (1 factor) or 1.8 months (≥2 factors; p < 0.001). The proposed score may aid in improved pre-therapeutic patient identification with (un-)favorable OS after RE and facilitate the balance between potential life prolongation and overaggressive patient selection.

Targeted Analysis of Cell-free Circulating Tumor DNA is Suitable for Early Relapse and Actionable Target Detection in Patients with Neuroblastoma.

PURPOSE: Treating refractory or relapsed neuroblastoma remains challenging. Monitoring body fluids for tumor-derived molecular information indicating minimal residual disease supports more frequent diagnostic surveillance and may have the power to detect resistant subclones before they give rise to relapses. If actionable targets are identified from liquid biopsies, targeted treatment options can be considered earlier. EXPERIMENTAL DESIGN: Droplet digital PCR assays assessing MYCN and ALK copy numbers and allelic frequencies of ALK p.F1174L and ALK p.R1275Q mutations were applied to longitudinally collected liquid biopsies and matched tumor tissue samples from 31 patients with high-risk neuroblastoma. Total cell-free DNA (cfDNA) levels and marker detection were compared with data from routine clinical diagnostics. RESULTS: Total cfDNA concentrations in blood plasma from patients with high-risk neuroblastoma were higher than in healthy controls and consistently correlated with neuron-specific enolase levels and lactate dehydrogenase activity but not with 123I-meta-iodobenzylguanidine scores at relapse diagnosis. Targeted cfDNA diagnostics proved superior for early relapse detection to all current diagnostics in 2 patients. Marker analysis in cfDNA indicated intratumor heterogeneity for cell clones harboring MYCN amplifications and druggable ALK alterations that were not detectable in matched tumor tissue samples in 17 patients from our cohort. Proof of concept is provided for molecular target detection in cerebrospinal fluid from patients with isolated central nervous system relapses. CONCLUSIONS: Tumor-specific alterations can be identified and monitored during disease course in liquid biopsies from pediatric patients with high-risk neuroblastoma. This approach to cfDNA surveillance warrants further prospective validation and exploitation for diagnostic purposes and to guide therapeutic decisions.

68Ga-DOTATOC-PET/MRI-A Secure One-Stop Shop Imaging Tool for Robotic Radiosurgery Treatment Planning in Patients with Optic Nerve Sheath Meningioma.

Optic nerve sheath meningiomas (ONSM) are rare but can lead to irreversible blindness. Hybrid imaging may enhance tumor delineation and diagnostic accuracy via receptor binding. However, relevant clinical data for ONSM are lacking. We evaluated the feasibility of receptor-based hybrid imaging prior to robotic radiosurgery (RRS). We retrospectively analyzed all of our institution's patients with suspected ONSM who underwent combined positron emission tomography and magnetic resonance imaging (PET/MRI) with gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) before RRS between 2018 and 2019. Eight patients with ten suspected ONSM (female = 7; median age, 51.2 years; IQR, 43.0-66.0) were included. Nine out of ten ONSM were deemed PET-positive with a median standard uptake value (SUV) max of 5.6 (IQR, 2.6-7.8). For all nine ONSM that presented 68Ga-DOTATOC uptake, hybrid PET/MRI was used for target volume contouring prior to RSS. At a median follow-up of 11.7 months (IQR, 9.4-16.4), tumor control was achieved in all patients. Radiosurgery resulted in the improvement of visual acuity in two of eight patients, whereas six showed stable vision. Ga68-DOTATOC-PET/MRI can be used for target volume contouring prior to RRS for ONSM as it enables safe treatment planning and improves diagnostic accuracy.

Selective Internal Radiation Therapy in Breast Cancer Liver Metastases: Outcome Assessment Applying a Prognostic Score.

Selective internal radiation therapy (SIRT) is a therapy option in patients with breast cancer liver metastasis (BCLM). This analysis aimed at identifying a prognostic score regarding overall survival (OS) after SIRT using routine pretherapeutic parameters. Retrospective analysis of 38 patients (age, 59 (39-84) years) with BCLM and 42 SIRT procedures. Cox regression for OS included clinical factors (age, ECOG and prior treatments), laboratory parameters, hepatic tumor load and dose reduction due to hepatopulmonary shunt. Elevated baseline ALT and/or AST was present if CTCAE grade ≥ 2 was fulfilled (>3 times the upper limit of normal). Median OS after SIRT was 6.4 months. In univariable Cox, ECOG ≥ 1 (hazard ratio (HR), 3.8), presence of elevated baseline ALT/AST (HR, 3.8), prior liver surgery (HR, 10.2), and dose reduction of 40% (HR, 8.1) predicted shorter OS (each p < 0.05). Multivariable Cox confirmed ECOG ≥ 1 (HR, 2.34; p = 0.012) and elevated baseline ALT/AST (HR, 4.16; p < 0.001). Combining both factors, median OS decreased from 19.2 months (0 risk factors; n = 14 procedures) to 5.9 months (1 factor; n = 20) or 2.2 months (2 factors; n = 8; p < 0.001). The proposed score may facilitate pretherapeutic identification of patients with unfavorable OS after SIRT. This may help to balance potential life prolongation with the hazards of invasive treatment and hospitalization.

Comparison of diagnostic value of 68 Ga-DOTATOC PET/MRI and standalone MRI for the detection of intracranial meningiomas.

To evaluate the diagnostic performance of magnetic resonance imaging (MRI) alone in comparison to positron emission tomography/ magnetic resonance imaging (PET/MRI) in patients with meningiomas. 57 patients with a total of 112 meningiomas of the brain were included. PET/MRI, including a fully diagnostic contrast enhanced MRI and PET, were acquired. PET/MRI was used as reference standard. The size and location of meningiomas was recorded. Likelihood-ratio chi-square tests were used to calculate p-values within logistic regression in order to compare different models. A multi-level logistic regression was applied to comply the hierarchical data structure. Multi-level regression adjusts for clustering in data was performed. The majority (n = 103) of meningiomas could be identified based on standard MRI sequences compared to PET/MRI. MRI alone achieved a sensitivity of 95% (95% CI 0.78, 0.99) and specificity of 88% (95% CI 0.58, 0.98). Based on intensity of contrast medium uptake, 97 meningiomas could be diagnosed with intense uptake (93.75%). Sensitivity was lowest with 74% for meningiomas < 0.5 cm3, high with 95% for meningiomas > 2cm3 and highest with 100% for meningiomas 0.5-1.0 cm3. Petroclival meningiomas showed lowest sensitivity with 88% compared to sphenoidal meningiomas with 94% and orbital meningiomas with 100%. Specificity of meningioma diagnostic with MRI was high with 100% for sphenoidal and hemispherical-dural meningiomas and meningiomas with 0.5-1.0 and 1.0-2.0 cm3. Overall MRI enables reliable detection of meningiomas compared to PET/MRI. PET/MRI imaging offers highest sensitivity and specificity for small or difficult located meningiomas.

Shortened Tracer Uptake Time in GA-68-DOTATOC-PET of Meningiomas Does Not Impair Diagnostic Accuracy and PET Volume Definition.

Ga-68-DOTATOC-PET/MRI can affect the planning target volume (PTV) definition of meningiomas before radiosurgery. A shorter tracer uptake time before image acquisition could allow the examination of more patients. The aim of this study was to investigate if shortening uptake time is possible without compromising diagnostic accuracy and PET volume. Fifteen patients (f = 12; mean age 52 years (34-80 years)) with meningiomas were prospectively examined with dynamic [68Ga]Ga-68-labeled [DOTA0-Phe1-Tyr3] octreotide (Ga-68-DOTATOC)-PET/MRI over 70 min before radiosurgery planning. Meningiomas were delineated manually in the PET dataset. PET volumes at each time point were compared to the reference standard 60 min post tracer injection (p.i.) using the Friedman test followed by a Wilcoxon signed-rank test and Bonferroni correction. In all patients, the earliest time point with 100% lesion detection compared to 60 min p.i. was identified. PET volumes did not change significantly from 15 min p.i. (p = 1.0) compared to 60 min p.i. The earliest time point with 100% lesion detection in all patients was 10 min p.i. In patients with meningiomas undergoing Ga-68-DOTATOC-PET, the tracer uptake time can safely be reduced to 15 min p.i. with comparable PET volume and 100% lesion detection compared to 60 min p.i.