To Perform, or Not to Perform Interim PET: Questioning the Impact of Midtherapy Evaluation During PRRT in GEP-NET Patients.

PURPOSE: This study aimed to analyze the impact of interim evaluation on the continuation of 177Lu-based peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to survey its usage across German university hospitals. PATIENTS AND METHODS: In 119 GEP-NET patients who underwent PRRT, we retrospectively assessed the results and therapeutic impact of restaging performed after 2 cycles using MRI/CT/somatostatin receptor imaging. Therapeutic decisions based on interim PET results were made in multidisciplinary tumor board meetings. Additionally, an online survey was conducted among 37 German university hospitals regarding their interim evaluation practices, focusing on the change in management. RESULTS: Of 119 patients, 83 completed 4 PRRT cycles; 36 stopped after 2: 27 showed PD, 3 had PR leading to surgery, 5 experienced toxicity, and 1 died. Those completing 4 cycles showed a median PFS of 38.0 months (95% confidence interval, 32.2-43.8). Seventeen of 37 surveyed hospitals routinely used interim evaluation. In a survey among 37 German university hospitals, 62% reported offering PRRT for GEP-NET patients, with 74% of these performing a routinely interim evaluation after 2 cycles of PRRT, primarily using PET/CT imaging techniques. CONCLUSIONS: Interim PET after 2 PRRT cycles helps to identify early progression in GEP-NET patients. Standardizing interim evaluation practices could enhance the comparability of clinical outcomes and optimize patient management.

68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT for locally advanced or recurrent pancreatic cancer staging and restaging after chemoradiotherapy.

Purpose: 68Ga-labeled fibroblast activation protein inhibitor (FAPI) is a novel PET tracer with great potential for staging pancreatic cancer. Data on locally advanced or recurrent disease is sparse, especially on tracer uptake before and after high dose chemoradiotherapy (CRT). The aim of this study was to evaluate [68Ga]Ga-FAPI-46 PET/CT staging in this setting. Methods: Twenty-seven patients with locally recurrent or locally advanced pancreatic adenocarcinoma (LRPAC n = 15, LAPAC n = 12) in stable disease or partial remission after chemotherapy underwent FAPI PET/CT and received consolidation CRT in stage M0 with follow-up FAPI PET/CT every three months until systemic progression. Quantitative PET parameters SUVmax, SUVmean, FAPI-derived tumor volume and total lesion FAPI-uptake were measured in baseline and follow-up PET/CT scans. Contrast-enhanced CT (ceCT) and PET/CT data were evaluated blinded and staged according to TNM classification. Results: FAPI PET/CT modified staging compared to ceCT alone in 23 of 27 patients in baseline, resulting in major treatment alterations in 52% of all patients (30%: target volume adjustment due to N downstaging, 15%: switch to palliative systemic chemotherapy only due to diffuse metastases, 7%: abortion of radiotherapy due to other reasons). Regarding follow-up scans, major treatment alterations after performing FAPI PET/CT were noted in eleven of 24 follow-up scans (46%) with switch to systemic chemotherapy or best supportive care due to M upstaging and ablative radiotherapy of distant lymph node and oligometastasis. Unexpectedly, in more than 90 % of the follow-up scans, radiotherapy did not induce local fibrosis related FAPI uptake. During the first follow-up, all quantitative PET metrics decreased, and irradiated lesions showed significantly lower FAPI uptake in locally controlled disease (SUVmax p = 0.047, SUVmean p = 0.0092) compared to local failure. Conclusion: Compared to ceCT, FAPI PET/CT led to major therapeutic alterations in patients with LRPAC and LAPAC prior to and after radiotherapy, which might help identify patients benefiting from adjustments in every treatment stage. FAPI PET/CT should be considered a useful diagnostic tool in LRPAC or LAPAC before and after CRT.

Keeping Up With ChatGPT: Evaluating Its Recognition and Interpretation of Nuclear Medicine Images.

PURPOSE: The latest iteration of GPT4 (generative pretrained transformer) is a large multimodal model that can integrate both text and image input, but its performance with medical images has not been systematically evaluated. We studied whether ChatGPT with GPT-4V(ision) can recognize images from common nuclear medicine examinations and interpret them. PATIENTS AND METHODS: Fifteen representative images (scintigraphy, 11; PET, 4) were submitted to ChatGPT with GPT-4V(ision), both in its Default and "Advanced Data Analysis (beta)" version. ChatGPT was asked to name the type of examination and tracer, explain the findings and whether there are abnormalities. ChatGPT should also mark anatomical structures or pathological findings. The appropriateness of the responses was rated by 3 nuclear medicine physicians. RESULTS: The Default version identified the examination and the tracer correctly in the majority of the 15 cases (60% or 53%) and gave an "appropriate" description of the findings or abnormalities in 47% or 33% of cases, respectively. The Default version cannot manipulate images. "Advanced Data Analysis (beta)" failed in all tasks in >90% of cases. A "major" or "incompatible" inconsistency between 3 trials of the same prompt was observed in 73% (Default version) or 87% of cases ("Advanced Data Analysis (beta)" version). CONCLUSIONS: Although GPT-4V(ision) demonstrates preliminary capabilities in analyzing nuclear medicine images, it exhibits significant limitations, particularly in its reliability (ie, correctness, predictability, and consistency).

Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.

BACKGROUND: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. METHODS: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. RESULTS: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan-Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7-27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2-15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6-21.8 months) with stable ALP values (Δ ± 10%). CONCLUSIONS: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.

ChatGPT: Can You Prepare My Patients for [18F]FDG PET/CT and Explain My Reports?

We evaluated whether the artificial intelligence chatbot ChatGPT can adequately answer patient questions related to [18F]FDG PET/CT in common clinical indications before and after scanning. Methods: Thirteen questions regarding [18F]FDG PET/CT were submitted to ChatGPT. ChatGPT was also asked to explain 6 PET/CT reports (lung cancer, Hodgkin lymphoma) and answer 6 follow-up questions (e.g., on tumor stage or recommended treatment). To be rated "useful" or "appropriate," a response had to be adequate by the standards of the nuclear medicine staff. Inconsistency was assessed by regenerating responses. Results: Responses were rated "appropriate" for 92% of 25 tasks and "useful" for 96%. Considerable inconsistencies were found between regenerated responses for 16% of tasks. Responses to 83% of sensitive questions (e.g., staging/treatment options) were rated "empathetic." Conclusion: ChatGPT might adequately substitute for advice given to patients by nuclear medicine staff in the investigated settings. Improving the consistency of ChatGPT would further increase reliability.

Hsp70-A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers.

Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal tumor biomarker. Since viable, mHsp70-positive tumor cells actively release Hsp70 in lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal tumor biomarker and its potential as an early predictive marker of therapeutic failure. We have also evaluated mHsp70 as a target for the isolation and enumeration of circulating tumor cells (CTCs) in patients with different tumor entities. Circulating vesicular Hsp70 levels were measured in the peripheral blood of tumor patients with the compHsp70 ELISA. CTCs were isolated using cmHsp70.1 and EpCAM monoclonal antibody (mAb)-based bead approaches and characterized by immunohistochemistry using cytokeratin and CD45-specific antibodies. In two out of 35 patients exhibiting therapeutic failure two years after initial diagnosis of non-metastatic breast cancer, progressively increasing levels of circulating Hsp70 had already been observed during therapy, whereas levels in patients without subsequent recurrence remained unaltered. With regards to CTC isolation from patients with different tumors, an Hsp70 mAb-based selection system appears superior to an EpCAM mAb-based approach. Extracellular and mHsp70 can therefore serve as a predictive biomarker for therapeutic failure in early-stage tumors and as a target for the isolation of CTCs in various tumor diseases.

Tibial Slope on Conventional Lateral Radiographs in Anterior Cruciate Ligament-Injured and Intact Knees: Mean Value and Outliers.

BACKGROUND: An increased tibial slope (TS) has been identified as a risk factor for anterior cruciate ligament (ACL) injury and graft failure after ACL reconstruction. However, different imaging modalities are used to determine the TS, resulting in divergent values. Consequently, no reference values and no consensus on thresholds can be reached, which in turn is mandatory for indicating correction osteotomies when facing outlier TS. PURPOSE: To determine the mean values of the TS and the incidence of their outliers in large cohorts of patients with ACL-injured and noninjured knees and to determine the feasibility of measuring TS on conventional lateral radiographs (CLRs). STUDY DESIGN: Cross-sectional study; Level of evidence 3. METHODS: TS of ACL-injured knees (n = 1000, group A) and ACL-intact knees (n = 1000, group B) was measured by 3 experienced examiners. Medial TS was measured on CLRs using the technique of Dejour and Bonnin. Patients with radiographs with poor image quality, osteoarthritis, previous osteotomies, or nondigital radiographs were excluded. The intra- and interrater reliability was calculated using the intraclass correlation coefficient. RESULTS: The mean TS was significantly higher in group A than in group B (10.04°± 3° [range, 2°-22°] vs 9.02°± 2.9° [range, 1°-18°], respectively; P < .001). Significantly more participants in group A had TS larger than 12° (≥12°, 32.2% vs 19.8%, P < .001; ≥13°, 20.9% vs 11.1%, P < .001; ≥14°, 13.5% vs 5.7%, P < .001; ≥15°, 8% vs 2.7%, P < .001; ≥16°, 3.7% vs 1.4%, P = .0005), respectively. In contrast, significantly more participatns in group B had TS 8° or less (≤8°, 32.1% vs 42.7%, P < .001; ≤7°, 20% vs 30.9%, P < .001; ≤6°, 12.4% vs 19.8%, P < .001; ≤5°, 6.6% vs 12%, P = .0003; ≤4°, 2.8% vs 5.3%, P = .0045). The intraclass correlation coefficient revealed a good to excellent reliability throughout measurements. CONCLUSION: Median values for the TS were 9° for uninjured and 10° for ACL-injured knees on CLRs. Notwithstanding its statistical significance, this finding might be negligible in clinical practice. However, a significantly larger number of outliers were found in the ACL-injured group exceeding a TS of 12° and demonstrating an incremental proportion with increasing TS, serving as a potential threshold for correction osteotomy. Furthermore, CLRs in the largest cohort to date exhibited high reproducibility, proving the feasibility of CLRs as a routine measurement for TS.

Same same but different: dopamine transporter SPECT on scanners with CZT vs. NaI detectors.

BACKGROUND: The aims of this study were to establish a normal database (NDB) for semiquantification of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with [123I]FP-CIT on a cadmium zinc telluride (CZT) camera, test the preexisting NaI-derived NDB for use in CZT scans, and compare the diagnostic findings in subjects imaged with a CZT scanner with either the preexisting NaI-based NDB or our newly defined CZT NDB. METHODS: The sample comprised 73 subjects with clinically uncertain parkinsonian syndrome (PS) who prospectively underwent [123I]FP-CIT SPECT on a CZT camera according to standard guidelines with identical acquisition and reconstruction protocols (DaTQUANT). Two experienced readers visually assessed the images and binarized the subjects into "non-neurodegenerative PS" and "neurodegenerative PS". Twenty-five subjects from the "non-neurodegenerative PS" subgroup were randomly selected to establish a CZT NDB. The remaining 48 subjects were defined as "test group". DaTQUANT was used to determine the specific binding ratio (SBR). For the test group, SBR values were transformed to z-scores for the putamen utilizing both the CZT NDB and the manufacturer-provided NaI-based NDB (GE NDB). A predefined fixed cut-off of -2 was used for dichotomization of z-scores to classify neurodegenerative and non-neurodegenerative PS. Performance of semiquantification using the two NDB to identify subjects with neurodegenerative PS was assessed in comparison with the visual rating. Furthermore, a randomized head-to-head comparison of both detector systems was performed semiquantitatively in a subset of 32 out of all 73 subjects. RESULTS: Compared to the visual rating as reference, semiquantification based on the dedicated CZT NDB led to fewer discordant ratings than the GE NDB in CZT scans (3 vs. 8 out of 48 subjects). This can be attributed to the putaminal z-scores being consistently higher with the GE NDB on a CZT camera (median absolute difference of 1.68), suggesting an optimal cut-off of -0.5 for the GE NDB instead of -2.0. Average binding ratios and z-scores were significantly lower in CZT compared to NaI data. CONCLUSIONS: Use of a dedicated, CZT-derived NDB is recommended in [123I]FP-CIT SPECT with a CZT camera since it improves agreement between semiquantification and visual assessment.

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.

Same same, but different? The neurological presentation of wildtype transthyretin (ATTRwt) amyloidosis.

BACKGROUND: Both hereditary transthyretin (ATTRv) amyloidosis and wildtype transthyretin (ATTRwt) amyloidosis can be associated with neurological diseases such as carpal tunnel syndrome and polyneuropathy. While ATTRv amyloidosis has been extensively studied, to date little is known about neurological complications of ATTRwt amyloidosis. In particular, the prevalence, pattern and extent of polyneuropathy and autonomic dysfunction has not been adequately investigated in the context of ATTRwt amyloidosis. To tackle this issue, we aimed to characterise the neurological presentation of ATTRwt amyloidosis and to compare between the presentations of ATTRv and ATTRwt amyloidoses. PATIENTS AND METHODS: Between November 2019 and September 2020, we included 50 patients with ATTRwt amyloidosis in this cohort study. All patients presented to the amyloidosis centre in Berlin, Germany and underwent neurological, cardiological and radiological work-up including neurological examination, laboratory testing, nerve conduction studies (NCS), echocardiography and scintigraphy. Patients were screened for symptoms of autonomic dysregulation and a subgroup of patients underwent tilt-table testing for orthostatic dysregulation. RESULTS: The cohort included 46 men and 4 women; the mean age of the study participants was 80.6 (standard deviation [SD] ± 5.0) years. All patients showed signs of cardiomyopathy on echocardiography. Neurological examination revealed peripheral, symmetric and length-depended predominately sensory polyneuropathy in 74% (n = 37) of patients. Neuropathy impairment scores (NIS) ranged from 0 to 50 with an average score of 8.4 (SD ± 10.1) indicating mild to moderate impairment. 90% and 92% of patients were classified as FAP stage I and PND stage I, respectively. Unilateral or bilateral carpal tunnel syndrome (CTS) was present in 70% (n = 35) and spinal stenosis was seen in 11% (n = 5) of patients. We detected a low rate of autonomic symptoms with a median COMPASS-31 total score of 18.4 points (IQR 32.4 points). Additional tilt-table testing of a subgroup of 8 patients yielded negative results for orthostatic intolerance. CONCLUSION: Distal-symmetric, predominantly sensory polyneuropathy is a common neurological complication in ATTRwt amyloidosis besides carpal tunnel syndrome and spinal stenosis, further substantiating the systemic character of the disease. Compared to ATTRv amyloidosis, the severity of polyneuropathy in ATTRwt amyloidosis is milder and without relevant motor involvement. Symptoms of autonomic dysfunction were not common in this cohort. Nevertheless, ATTRwt amyloidosis is a treatable disease and should be included in the differential diagnosis of sensory polyneuropathy in the elderly.

Analysis of cartilage injury patterns and risk factors for knee joint damage in patients with primary lateral patella dislocations.

BACKGROUND: Lateral patellar dislocation (LPD) frequently causes damage to the knee. Injury patterns and risk factors contributing to such injuries have not yet been examined in detail. METHODS: We retrospectively analyzed 50 consecutive patients with primary LPD. Two reviewers evaluated the MRI images regarding risk factors for LPD (Dejours classification; Caton-Deschamps Index, CDI; distance from the tibial tuberosity to trochlear groove, TT-TG; trochlear depth, TD) as well as joint damages according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS). RESULTS: 33 male and 17 female patients with a mean age of 23.2 (±9.6) years were included in this study. 52% were classified Dejours ≥ B, 34% had a CDI ≥ 1.3, 22% a TT-TG ≥ 20mm and 52% a TD < 3mm. 49 out of 50 patients (98%) showed abnormalities according to WORMS. The most frequently observed abnormalities were synovitis/effusion (49/50, 98%), bone marrow oedema (44/50, 88%) and cartilage damage (42/50, 84%). Most frequently affected subregions were medial (41/50, 82%) and lateral (31/50, 62%) patella as well as the anterior (43/50, 86%), central (42/50, 84%) and posterior (11/50, 22%) portion of the lateral femoral condyle. There was no significant correlation between any of the examined risk factors and joint damages according to WORMS. Male patients had higher scores regarding total cartilage damage (5.11 vs. 2.56, p = 0.029), total score for the lateral femorotibial joint (3.15 vs. 1.65, p = 0.026) and overall total WORMS score (12.15 vs. 8.29, p = 0.038). CONCLUSION: Risk factors for LPD do not influence the risk of damages to the knee joint after primary LPD. Although LPD is generally known to affect more female than male patients, male patients suffered more severe injuries after primary LPD, particularly of the lateral femorotibial joint. Overall, our results underline the importance of MRI imaging after primary LPD.

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.

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

An optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis.

BACKGROUND: In [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°). METHODS: In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i. RESULTS: In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence. CONCLUSIONS: Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

Respiratory motion correction for enhanced quantification of hepatic lesions in simultaneous PET and DCE-MR imaging.

Simultaneous positron-emission tomography (PET)-magnetic resonance (MR) imaging is a hybrid technique in oncological hepatic imaging combining soft-tissue and functional contrast of dynamic contrast enhanced MR (DCE-MR) with metabolic information from PET. In this context, respiratory motion represents a major challenge by introducing blurring, artifacts and misregistration in the liver. In this work, we propose a free-breathing 3D non-rigid respiratory motion correction framework for simultaneously acquired DCE-MR and PET data, which makes use of higher spatial resolution MR data to derive motion information used directly during image reconstruction to minimize image blurring and motion artifacts. The main aim was to increase contrast of hepatic metastases to improve their detection and characterization. DCE-MR data were acquired at 3T through a golden radial phase encoding scheme, enabling derivation of motion fields. These were used in the motion compensated image reconstruction of DCE-MR time-series (48 time-points, 6 s temporal resolution, 1.5 mm isotropic spatial resolution) and 3D PET activity map, which was subsequently interpolated to the DCE-MR resolution. The extended Tofts model was fitted to DCE-MR data, obtaining functional parametric maps related to perfusion such as the endothelial permeability (Kt). Fifty-seven hepatic metastases were identified and analyzed. Quantitative evaluations of motion correction in PET images demonstrated average percentage increases of 16% ± 5% (mean ± SD) in Contrast (C), 18% ± 6% in SUVmeanand 14% ± 2% in SUVmax, while DCE-MR andKtscored contrast-to-noise-ratio increases of 64% ± 3% and 90% ± 6%, respectively. Motion-corrected data visually showed improved image contrast of hepatic metastases and effectively reduced blurring and motion artefacts. Scatter plots of SUVmeanversusKtsuggested that the proposed framework improved differentiation ofKtmeasurements. The presented motion correction framework for simultaneously acquired PET-DCE-MR data provides accurately aligned images with increased contrast of hepatic lesions allowing for improved detection and characterization.

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.

The Prognostic Value of the De Ritis Ratio for Progression-Free Survival in Patients with NET Undergoing [177Lu]Lu-DOTATOC-PRRT: A Retrospective Analysis.

BACKGROUND: The De Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) has demonstrated prognostic value in various cancer entities. We evaluated the prognostic capability of the De Ritis ratio in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). METHODS: Unicentric, retrospective analysis of 125 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC (female: 37%; median age: 66 years; G1+G2 NET: 95%). The prognostic value regarding progression-free survival (PFS) was analyzed with univariable and multivariable Cox regression. Prognostic accuracy was determined with Harrell's C index and a likelihood ratio test. RESULTS: Progression, relapse, or death after PRRT was observed in 102/125 patients. Median progression-free survival (PFS) was 15.8 months. Pancreatic or pulmonary origin, high De Ritis ratio, and high Chromogranin A (CgA) significantly predicted shorter PFS in univariable Cox. In multivariable Cox regression, only high De Ritis ratio >0.927 (HR: 1.7; p = 0.047) and high CgA >twice the upper normal limit (HR: 2.1; p = 0.005) remained independent predictors of shorter PFS. Adding the De Ritis ratio to the multivariable Cox model (age, Eastern Cooperative Oncology Group (ECOG) performance status, primary origin, CgA) significantly improved prognostic accuracy (p < 0.001). CONCLUSIONS: The De Ritis ratio is simple to obtain in clinical routine and can provide independent prognostic value for PFS in patients with NET undergoing PRRT.

A rare case of a patient with a high grade neuroendocrine tumor developing neutropenic sepsis after receiving PRRT combined with Capecitabine or Temozolomide: A case report.

Neuroendocrine tumors (NET) are rare and demonstrate variable clinical behavior depending on the degree of tumor differentiation. Patients with poorly differentiated tumors (NET G3) have a poor prognosis. Systemic treatment with cytotoxic chemotherapy is considered to be the treatment of choice. In patients that are refractory or intolerant to first-line therapy, experts recommend peptide receptor radionuclide therapy (PRRT) in tumors that express somatostatin receptors. Recently, combinations of PRRT and chemotherapy were tested in patients with NET. Available data have reported promising tumor control rates and an excellent toxicity profile in cases where PRRT had been administered with capecitabine/temozolomide, even when administered as salvage therapy. The current study reported an exceptional case of advanced NET G3 with severe toxicity upon receiving PRRT in combination with capecitabine/temozolomide as third line therapy. The patient developed a life-threatening neutropenic fever, fungal pneumonia and necrotizing mastitis 23 days after the first cycle of therapy was administered. However, the treatment led to a significant reduction in tumor size. A total of 5 months after treatment initiation, the patient was alive and in excellent clinical condition with sustained tumor response. In summary, the current study presented a rare case of high grade NET exhibiting an almost complete response to PRRT in combination capecitabine/temozolomide, despite facing unexpected severe toxicity.