Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery.

BACKGROUND AND OBJECTIVE: Respiratory muscle activity is increased in patients with chronic respiratory disease. 18 F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value? METHODS: Patients undergoing 18 F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort. RESULTS: One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51-2.25], sternocleidomastoid 1.64 [1.34-1.95], intercostal 1.01 [0.84-1.16], diaphragm 1.79 [1.41-2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r = -0.29, p < 0.001) and SCM (r = -0.17, p = 0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r = 0.17, p = 0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO2 max (15.4 [14.2-17.5] vs. 17.2 mL/kg/min [15.2-21.1], p = 0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01). CONCLUSION: Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. 18 F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.

Deep learning analysis of contrast-enhanced spectral mammography to determine histoprognostic factors of malignant breast tumours.

OBJECTIVE: To evaluate if a deep learning model can be used to characterise breast cancers on contrast-enhanced spectral mammography (CESM). METHODS: This retrospective mono-centric study included biopsy-proven invasive cancers with an enhancement on CESM. CESM images include low-energy images (LE) comparable to digital mammography and dual-energy subtracted images (DES) showing tumour angiogenesis. For each lesion, histologic type, tumour grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER-2 status, Ki-67 proliferation index, and the size of the invasive tumour were retrieved. The deep learning model used was a CheXNet-based model fine-tuned on CESM dataset. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated for the different models: images by images and then by majority voting combining all the incidences for one tumour. RESULTS: In total, 447 invasive breast cancers detected on CESM with pathological evidence, in 389 patients, which represented 2460 images analysed, were included. Concerning the ER, the deep learning model on the DES images had an AUC of 0.83 with the image-by-image analysis and of 0.85 for the majority voting. For the triple-negative analysis, a high AUC was observable for all models, in particularity for the model on LE images with an AUC of 0.90 for the image-by-image analysis and 0.91 for the majority voting. The AUC for the other histoprognostic factors was lower. CONCLUSION: Deep learning analysis on CESM has the potential to determine histoprognostic tumours makers, notably estrogen receptor status, and triple-negative receptor status. KEY POINTS: • A deep learning model developed for chest radiography was adapted by fine-tuning to be used on contrast-enhanced spectral mammography. • The adapted models allowed to determine for invasive breast cancers the status of estrogen receptors and triple-negative receptors. • Such models applied to contrast-enhanced spectral mammography could provide rapid prognostic and predictive information.

Characterization of positioning uncertainties in PET-CT-MR trimodality solutions for radiotherapy.

The purpose of this study was to evaluate the positioning uncertainties of two PET/CT-MR imaging setups, C1 and C2. Because the PET/CT data were acquired on the same hybrid device with automatic image registration, experiments were conducted using CT-MRI data. In C1, a transfer table was used, which allowed the patient to move from one imager to another while maintaining the same position. In C2, the patient stood up and was positioned in the same radiotherapy treatment position on each imager. The two setups provided a set of PET/CT and MR images. The accuracy of the registration software was evaluated on the CT-MRI data of one patient using known translations and rotations of MRI data. The uncertainties on the two setups were estimated using a phantom and a cohort of 30 patients. The accuracy of the positioning uncertainties was evaluated using descriptive statistics and a t-test to determine whether the mean shift significantly deviated from zero (p < 0.05) for each setup. The maximum registration errors were less than 0.97 mm and 0.6° for CT-MRI registration. On the phantom, the mean total uncertainties were less than 2.74 mm and 1.68° for C1 and 1.53 mm and 0.33° for C2. For C1, the t-test showed that the displacements along the z-axis did not significantly deviate from zero (p = 0.093). For C2, significant deviations from zero were present for anterior-posterior and superior-inferior displacements. The mean total uncertainties were less than 4 mm and 0.42° for C1 and less than 1.39 mm and 0.27° for C2 in the patients. Furthermore, the t-test showed significant deviations from zero for C1 on the anterior-posterior and roll sides. For C2, there was a significant deviation from zero for the left-right displacements.This study shows that transfer tables require careful evaluation before use in radiotherapy.

Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study.

The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients] were assessed in this non-interventional study. Median age of the patients was 33.5 years (range 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype are correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, NA=6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). Mean of DeltaSUVmax after C2 was -78.8%. We analyzed ctDNA after C2 for 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.

Radiotherapy boost in patients with hypoxic lesions identified by 18F-FMISO PET/CT in non-small-cell lung carcinoma: can we expect a better survival outcome without toxicity? [RTEP5 long-term follow-up].

PURPOSE: Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfactory survival, partially due to radiation resistance in hypoxic tissues. The objective was to update survival and toxicity at 3 years following radiotherapy boost to hypoxic tumours in NSCLC patients treated with curative-intent chemoradiotherapy. METHODS: This was an open-label, nonrandomized, multicentre, phase II clinical trial. 18F-Fluoromisonidazole (18F-FMISO) PET/CT was used to determine the hypoxic profile of the patients. 18F-FMISO-positive patients and those without organ-at-risk constraints received a radiotherapy boost (70-84 Gy); the others received standard radiotherapy (66 Gy). Overall survival (OS), progression-free survival (PFS) and safety were assessed. RESULTS: A total of 54 patients were evaluated. OS and PFS rates at 3 years were 48.5% and 28.8%, respectively. The median OS in the 18F-FMISO-positive patients was 25.8 months and was not reached in the 18F-FMISO-negative patients (p = 0.01). A difference between the groups was also observed for PFS (12 months vs. 26.2 months, p = 0.048). In 18F-FMISO-positive patients, no difference was observed in OS in relation to dose, probably because of the small sample size (p = 0.30). However, the median OS seemed to be in favour of patients who received the radiotherapy boost (26.5 vs. 15.3 months, p = 0.71). In patients who received the radiotherapy boost, no significant late toxicities were observed. CONCLUSION: 18F-FMISO uptake in NSCLC patients is strongly associated with features indicating a poor prognosis. In 18F-FMISO-positive patients, the radiotherapy boost seemed to improve the OS by 11.2 months. A further clinical trial is needed to investigate the efficacy of a radiotherapy boost in patients with hypoxic tumours.

Anthropometer3D: Automatic Multi-Slice Segmentation Software for the Measurement of Anthropometric Parameters from CT of PET/CT.

Anthropometric parameters like muscle body mass (MBM), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) are used in oncology. Our aim was to develop and evaluate the software Anthropometer3D measuring these anthropometric parameters on the CT of PET/CT. This software performs a multi-atlas segmentation of CT of PET/CT with extrapolation coefficients for the body parts beyond the usual acquisition range (from the ischia to the eyes). The multi-atlas database is composed of 30 truncated CTs manually segmented to isolate three types of voxels (muscle, fat, and visceral fat). To evaluate Anthropomer3D, a leave-one-out cross-validation was performed to measure MBM, FBM, LBM, VAT, and SAT. The reference standard was based on the manual segmentation of the corresponding whole-body CT. A manual segmentation of one CT slice at level L3 was also used. Correlations were analyzed using Dice coefficient, intra-class coefficient correlation (ICC), and Bland-Altman plot. The population was heterogeneous (sex ratio 1:1; mean age 57 years old [min 23; max 74]; mean BMI 27 kg/m2 [min 18; max 40]). Dice coefficients between reference standard and Anthropometer3D were excellent (mean+/-SD): muscle 0.95 ± 0.02, fat 1.00 ± 0.01, and visceral fat 0.97 ± 0.02. The ICC was almost perfect (minimal value of 95% CI of 0.97). All Bland-Altman plot values (mean difference, 95% CI and slopes) were better for Anthropometer3D compared to L3 level segmentation. Anthropometer3D allows multiple anthropometric measurements based on an automatic multi-slice segmentation. It is more precise than estimates using L3 level segmentation.

Correction to: Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma.

A unit error concerning the tumor volume surface ratio (TVSR) is present throughout the article. The unit reported is "cm" but is actually "mm".

Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma.

INTRODUCTION: Our aim was to study the prognostic value of two new 18F-FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). We examined the total tumor surface (TTS), describing the tumor-host interface, and the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation. METHODS: We retrospectively included 215 patients with DLBCL. Patients underwent initial 18F-FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimens (27%). The TMTV was measured using a fixed threshold value of 41% of SUVmax. To calculate TTS and TVSR, the surface was measured using an in-house software based on the marching cube algorithm. Spearman's rank correlation coefficient (ρ) was computed between TMTV, TTS, and TVSR, and ROC analysis was performed. Survival functions at 5 years were studied using a Kaplan-Meier method and uni/multivariate Cox analysis. RESULTS: TVSR was poorly correlated with TMTV (ρ = 0.5) and TTS (ρ = 0.26), while TTS was highly correlated with TMTV (ρ = 0.94) and was, therefore, excluded from the analysis. TMTV had the highest area under the ROC curve (0.711) and the best sensitivity (0.797), while TVSR had the best specificity (0.745). The optimal cut-off values to predict 5-year OS were 222 cm3 for TMTV and 6.0 mm for TVSR. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining the International Prognostic Index (IPI), the type of chemotherapy, TMTV, and TVSR, all parameters were independent and significant prognostic factors (HR [95%CI]: IPI 1.4 [1.1-1.8], type of chemotherapy 4.5 [2.0-10.5], TMTV 2.8 [1.4-5.5], TVSR 2.1 [1.3-3.4]). A synergistic effect between TMTV and TVSR was observed in a Kaplan-Meier analysis combining the two parameters. CONCLUSIONS: TVSR measured on the initial 18F-FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy.

How to use PET/CT in the evaluation of response to radiotherapy.

Radiotherapy is a major treatment modality for many cancers. Tumor response after radiotherapy determines the subsequent steps of the patient's management (surveillance, adjuvant or salvage treatment and palliative care). Tumor response assessed during radiotherapy offers a promising opportunity to adapt the treatment plan to reduced or increased target volume, to specifically target sub-volumes with relevant biological characteristics (metabolism, hypoxia, proliferation, etc.) and to further spare the organs at risk. In addition to its role in the diagnosis and the initial staging, Positron Emission Tomography combined with a Computed Tomography (PET/CT) provides functional information and is therefore attractive to evaluate tumor response. The aim of this paper is to review the published data addressing PET/CT as an evaluation tool in irradiated tumors. Reports on PET/CT acquired at various times (during radiotherapy, after initial (chemo-) radiotherapy, after definitive radiotherapy and during posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus, prostate and rectum) were collected and reviewed. Various tracers and technical aspects are also discussed. 18F-FDG PET/CT has a well-established role in clinical routine after definitive chemo-radiotherapy for locally advanced head-and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances and the clinical benefits of assessing tumor response with PET/CT remain a field of very active research. The combination of PET with Magnetic Resonance Imaging (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor response can be evaluated by PET/CT with clinical consequences in multiple situations, notably in head and neck and prostate cancers, after radiotherapy. Further clinical evaluation for most cancers is still needed, possibly in association to MRI.

Automatic Measurement of the Total Visceral Adipose Tissue From Computed Tomography Images by Using a Multi-Atlas Segmentation Method.

BACKGROUND: The visceral adipose tissue (VAT) volume is a predictive and/or prognostic factor for many cancers. The objective of our study was to develop an automatic measurement of the whole VAT volume using a multi-atlas segmentation (MAS) method from a computed tomography. METHODS: A total of 31 sets of whole-body computed tomography volume data were used. The reference VAT volume was defined on the basis of manual segmentation (VATMANUAL). We developed an algorithm, which measured automatically the VAT volumes using a MAS based on a nonrigid volume registration algorithm coupled with a selective and iterative method for performance level estimation (SIMPLE), called VATMAS_SIMPLE. The results were evaluated using intraclass correlation coefficient and dice similarity coefficients. RESULTS: The intraclass correlation coefficient of VATMAS_SIMPLE was excellent, at 0.976 (confidence interval, 0.943-0.989) (P < 0.001). The dice similarity coefficient of VATMAS_SIMPLE was also good, at 0.905 (SD, 0.076). CONCLUSIONS: This newly developed algorithm based on a MAS can measure accurately the whole abdominopelvic VAT.

The phenotypical core of Alzheimer's disease-related and nonrelated variants of the corticobasal syndrome: A systematic clinical, neuropsychological, imaging, and biomarker study.

INTRODUCTION: The corticobasal syndrome (CBS) constitutes a neurodegenerative disease spectrum with substantial phenotypical or biological heterogeneity, requiring large or multimodal studies to identify its clinico-biological signature while disentangling Alzheimer's disease (AD)-related from non-AD-related CBS. METHODS: We analyzed a large (N = 45) monocenter expert-clinic CBS cohort, recruited in motor and/or cognitive units to avoid recruitment biases, assessed with standardized motor and/or cognitive-language tests, brain perfusion imaging, and cerebrospinal fluid biomarkers. RESULTS: CBS mainly manifests as a motor and/or language disorder incorporating a "mixed progressive aphasia" phenotype, consistent with left-lateralized damage to frontal-parietal-temporal cortices. Biomarker expression indicates in 18% underlying AD causing predominant parietal-temporal damage and Gerstmann syndrome (sensitivity 75%; specificity 75%), whereas non-AD-CBS presented with predominant prefrontal and lexical-semantic impairment. DISCUSSION: CBS is primarily a "motor-plus-aphasia" disease unfolding into AD-related and non-AD-related variants with distinctive cognitive-anatomic patterns. CBS, and notably its "Gerstmann variant", should be included in the new AD "lexicon" and categorized in the evolving diagnostic spectrum of "atypical AD"d.

Cerebellum/liver index on baseline 18F-FDG PET/CT to improve prognostication in post-transplant lymphoproliferative disorders: a multicenter retrospective study.

BACKGROUND: Besides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses. RESULTS: A total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0-4.0) and 2.4 (1.3-4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 (p = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS. CONCLUSION: CLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.

Trifluridine/tipiracil + oxaliplatin ± nivolumab vs FOLFOX ± nivolumab in HER2 negative advanced oesogastric adenocarcinoma: The PRODIGE73-UCGI40-LOGICAN trial.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile. AIMS: The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab. METHODS: This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5. DISCUSSION: PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796).

Advances in PET and MRI imaging of tumor hypoxia.

Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.

The impact of sarcopenia on survival and treatment tolerance in patients with head and neck cancer treated with chemoradiotherapy.

BACKGROUND: Sarcopenia appears to be a negative prognostic factor for poor survival outcomes and worse treatment tolerance in patients with head-and-neck squamous cell carcinoma (HNSCC). We evaluated sarcopenia's impact on overall survival (OS), disease-free survival (DFS) and chemo-radiation tolerance in patients with head-and-neck cancer (HNC) treated with chemoradiotherapy (CRT) from a monocentric observational study. METHODS: We identified patients with HNC treated by CRT between 2009 and 2018 with pretreatment imaging using positron emission tomography-computed tomography scans (PET/CT). Sarcopenia was measured using the pretreatment PET/CT at the L3 vertebral body using previously published methods. Clinical variables were retrospectively retrieved. RESULTS: Of 216 patients identified, 54 patients (25.47%) met the criteria for sarcopenia. These patients had a lower mean body mass index before treatment (21.92 vs. 25.65 cm/m2 , p < 0.001) and were more likely to have a history of smoking (88.89% vs. 71.52%, p = 0.01), alcohol use (55.56% vs. 38.61%, p = 0.03) and positive human papilloma virus status (67.74% vs. 41.75%, p = 0.011). At 3 years of follow-up, OS and DFS were 75% and 70% versus 82% and 85% for sarcopenic and non-sarcopenic patients, respectively (p = 0.1 and p = 0.00015). On multivariate analysis, sarcopenia appeared as a pejorative factor on DFS (hazard ratio 2.174, p = 0.0001) in the overall cohort. Sarcopenic patients did not require more chemotherapy and radiation-treatment interruptions and did not suffer from more chemo-induced and radiation-induced grade 3-4 toxicities than their non-sarcopenic counterparts. CONCLUSION: Sarcopenia in HNSCC patients is an independent adverse prognostic factor for DFS after definitive chemoradiotherapy.

Anti-leucine-rich glioma-inactivated 1 encephalitis revealed by a manic episode: insights from frontal lobe dysfunction in neuropsychiatry through neuropsychology and metabolic imaging. A case report.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a limbic encephalitis that rarely presents as an isolated psychiatric syndrome. Case presentation: A 70-year-old patient first presented with behavioral disorder including hyperactivity, euphoria, with disinhibition and accelerated speech associated with severe insomnia and cognitive disorder. A manic episode was diagnosed and he received various psychotropic medications with no improvement. Invesitgations were negative (MRI showed T2 aspecific hyperintensities with no hyperintensities in limbic regions and EEG was normal). He was transferred to a nursing home, with a diagnosis of neurodegenerative condition. Later, he was referred to our unit for further investigations. A cerebral 18F-FDG-PET revealed an association of frontal hypometabolism and temporal and striatum hypermetabolism and CSF analysis revealed slightly increased white blood cell counts. Plasmatic anti-LGI1 antibodies were detected. The patient was treated with intra-venous immunoglobulin (IvIg) but showed no improvement. Second-line treatment (a combination of rituximab and cyclophosmphamide) was then administered for a year, leading to an improvement of neuropsychiatric symptoms and normalization of metabolic impairment on 18F-FDG-PET. Conclusion: In this report, we describe a novel case of a patient withanti-LGI1 encephalitis with a predominant long-term psychiatric presentation. An atypical presentation (such as atypical psychiatric symptoms, neurocognitive disorder, and hyponatremia) should prompt further investigations such as CSF analysis, considering that MRI and EEG may be normal. FDG-PET might be of interest but few data are available in the literature. Early treatment of anti-LGI1 encephalitis is crucial for overall prognosis and may delay the development of dementia in some cases.

Body Composition to Define Prognosis of Cancers Treated by Anti-Angiogenic Drugs.

Background: Body composition could help to better define the prognosis of cancers treated with anti-angiogenics. The aim of this study is to evaluate the prognostic value of 3D and 2D anthropometric parameters in patients given anti-angiogenic treatments. Methods: 526 patients with different types of cancers were retrospectively included. The software Anthropometer3DNet was used to measure automatically fat body mass (FBM3D), muscle body mass (MBM3D), visceral fat mass (VFM3D) and subcutaneous fat mass (SFM3D) in 3D computed tomography. For comparison, equivalent two-dimensional measurements at the L3 level were also measured. The area under the curve (AUC) of the receiver operator characteristics (ROC) was used to determine the parameters' predictive power and optimal cut-offs. A univariate analysis was performed using Kaplan−Meier on the overall survival (OS). Results: In ROC analysis, all 3D parameters appeared statistically significant: VFM3D (AUC = 0.554, p = 0.02, cutoff = 0.72 kg/m2), SFM3D (AUC = 0.544, p = 0.047, cutoff = 3.05 kg/m2), FBM3D (AUC = 0.550, p = 0.03, cutoff = 4.32 kg/m2) and MBM3D (AUC = 0.565, p = 0.007, cutoff = 5.47 kg/m2), but only one 2D parameter (visceral fat area VFA2D AUC = 0.548, p = 0.034). In log-rank tests, low VFM3D (p = 0.014), low SFM3D (p < 0.0001), low FBM3D (p = 0.00019) and low VFA2D (p = 0.0063) were found as a significant risk factor. Conclusion: automatic and 3D body composition on pre-therapeutic CT is feasible and can improve prognostication in patients treated with anti-angiogenic drugs. Moreover, the 3D measurements appear to be more effective than their 2D counterparts.

Synergic prognostic value of 3D CT scan subcutaneous fat and muscle masses for immunotherapy-treated cancer.

BACKGROUND: Our aim was to explore the prognostic value of anthropometric parameters in a large population of patients treated with immunotherapy. METHODS: We retrospectively included 623 patients with advanced non-small cell lung cancer (NSCLC) (n=318) or melanoma (n=305) treated by an immune-checkpoint-inhibitor having a pretreatment (thorax-)abdomen-pelvis CT scan. An external validation cohort of 55 patients with NSCLC was used. Anthropometric parameters were measured three-dimensionally (3D) by a deep learning software (Anthropometer3DNet) allowing an automatic multislice measurement of lean body mass, fat body mass (FBM), muscle body mass (MBM), visceral fat mass (VFM) and sub-cutaneous fat mass (SFM). Body mass index (BMI) and weight loss (WL) were also retrieved. Receiver operator characteristic (ROC) curve analysis was performed and overall survival was calculated using Kaplan-Meier (KM) curve and Cox regression analysis. RESULTS: In the overall cohort, 1-year mortality rate was 0.496 (95% CI: 0.457 to 0.537) for 309 events and 5-year mortality rate was 0.196 (95% CI: 0.165 to 0.233) for 477 events. In the univariate Kaplan-Meier analysis, prognosis was worse (p<0.001) for patients with low SFM (<3.95 kg/m2), low FBM (<3.26 kg/m2), low VFM (<0.91 kg/m2), low MBM (<5.85 kg/m2) and low BMI (<24.97 kg/m2). The same parameters were significant in the Cox univariate analysis (p<0.001) and, in the multivariate stepwise Cox analysis, the significant parameters were MBM (p<0.0001), SFM (0.013) and WL (0.0003). In subanalyses according to the type of cancer, all body composition parameters were statistically significant for NSCLC in ROC, KM and Cox univariate analysis while, for melanoma, none of them, except MBM, was statistically significant. In multivariate Cox analysis, the significant parameters for NSCLC were MBM (HR=0.81, p=0.0002), SFM (HR=0.94, p=0.02) and WL (HR=1.06, p=0.004). For NSCLC, a KM analysis combining SFM and MBM was able to separate the population in three categories with the worse prognostic for the patients with both low SFM (<5.22 kg/m2) and MBM (<6.86 kg/m2) (p<0001). On the external validation cohort, combination of low SFM and low MBM was pejorative with 63% of mortality at 1 year versus 25% (p=0.0029). CONCLUSIONS: 3D measured low SFM and MBM are significant prognosis factors of NSCLC treated by immune checkpoint inhibitors and can be combined to improve the prognostic value.

Baseline 18F-FDG Metabolic Tumor Volume Predicts Response to Rituximab Induction in Post-transplant Lymphoproliferative Disorders: A Multi-institutional Retrospective Study.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression. Sequential treatment is commonly proposed, combining induction with rituximab (R-induction) followed by either continuation of treatment or addition of chemotherapy depending on response. Response to R-induction, often assessed by CT scan, is a major predictor of overall survival (OS). The aim of the study was to analyze predictive factors of R-induction response, including total metabolic tumor volume (TMTV), and investigate the role of 18F-FDG PET/CT in response assessment. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. Only patients treated by R-induction with a baseline 18F-FDG PET/CT were included. Response to R-induction was assessed by 18F-FDG PET/CT. The optimal threshold of TMTV for rituximab response was determined using receiver operating characteristic curves. Univariate and multivariate analyses were conducted to identify predictive factors of response. A total of 67 patients were included. Survival characteristics were similar to those previously reported: the complete response rate to R-induction was 30%, the 3-year OS estimate was 66%, and the treatment-related mortality was 4%. The optimal threshold for TMTV to predict R-induction response was 135 cm3. The response rate to R-induction was 38% in the 21 patients with TMTV ≥ 135 cm3 and 72% in the 46 patients with TMTV < 135 cm3. TMTV was a significant predictor of response, both at univariate and multivariate analyses (odd ratios = 3.71, P = 0.022). Baseline TMTV is predictive of response to R-induction. Early assessment of patient response is feasible with 18F-FDG PET/CT.

High prevalence of pre-existing sarcopenia in critically ill patients with hematologic malignancies admitted to the intensive care unit for sepsis or septic shock.

BACKGROUND & AIMS: We aimed to evaluate body composition (BC) by computed tomography (CT) in hematologic malignancy (HM) patients admitted to the intensive care unit (ICU) for sepsis or septic shock. METHODS: We retrospectively assessed BC and its impact on outcome of 186 patients at the 3rd lumbar (L3) and 12th thoracic vertebral levels (T12) using CT-scan performed before ICU admission. RESULTS: The median patient age was 58.0 [47; 69] years. Patients displayed adverse clinical characteristics at admission with median [q1; q3] SAPS II and SOFA scores of 52 [40; 66] and 8 [5; 12], respectively. The mortality rate in the ICU was 45.7%. Overall survival rates at 1 month after admission in the pre-existing sarcopenic vs. non pre-existing sarcopenic patients were 47.9% (95% CI [37.6; 61.0]) and 55.0% (95% CI [41.6; 72.8]), p = 0.99), respectively, at the L3 level and 48.4% (95% CI [40.4; 58.0]) vs. 66.7% (95% CI [51.1; 87.0]), p = 0.062), respectively, at the T12 level. CONCLUSIONS: Sarcopenia is assessable by CT scan at both the T12 and L3 levels and is highly prevalent in HM patients admitted to the ICU for severe infections. Sarcopenia may contribute to the high mortality rate in the ICU in this population.