Intra-arterial administration of PSMA-targeted radiopharmaceuticals for brain tumors: is the era of interventional theranostics next?

In recent years, prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, has emerged as a promising biomarker for theranostics, integrating diagnosis and therapy. PSMA's overexpression in various tumors, including brain metastases and high-grade gliomas, suggests its potential in neuro-oncology. Pruis et al. conducted a proof-of-concept study comparing intra-arterial (IA) and intravenous (IV) administration of 68Ga-PSMA-11 in brain tumor patients, aiming to enhance radioligand therapy (RLT) outcomes. Ten patients underwent IV and super-selective IA (ssIA) tracer administration, showing higher tumor uptake and more favorable biodistribution after ssIA administration on positron emission tomography (PET). Dosimetry modeling on the basis of PET data resulted in median absorbed radiation doses per tumor per cycle notably higher with ssIA with respect to IV administration, indicating its potential for RLT optimization. Challenges persist, notably in penetrating intact blood-brain barriers and targeting tumor cells effectively. To overcome these limitations, novel approaches like convection-enhanced delivery and focused ultrasound warrant exploration. Safety concerns, though minimal in this study, underscore the need for larger trials and AI-assisted procedures. PSMA's role in neuro-oncological theranostics is promising, but future research must address specificity and compare it with emerging targets.

Ensemble machine learning to predict futile recanalization after mechanical thrombectomy based on non-contrast CT imaging.

OBJECTIVES: Despite successful recanalization after Mechanical Thrombectomy (MT), approximately 25 % of patients with Acute Ischemic Stroke (AIS) due to Large Vessel Occlusion (LVO) show unfavorable clinical outcomes, namely Futile Recanalization (FR). We aimed to use a Machine Learning (ML) Non-Contrast brain CT (NCCT) imaging predictive model to identify FR in patients undergoing MT. MATERIALS & METHODS: Between July 2022 and December 2022, 70 consecutive patients with LVO undergoing a complete recanalization (eTICI 3) with MT within 8 h from onset at our Centre were analyzed. Two NCCT images per patient of middle cerebral artery vascular territory and patients' clinical characteristics were classified by the presence of ischemic features on 24 h NCCT after MT. Each slice was segmented with "Mazda" software ver.4.6 by placing a Region Of Interest (ROI) on the whole brain by two radiologists in consensus. A total of 381 features were extracted for each slice. The dataset was split into train and test set with a 70:30 ratio. RESULTS: Eleven classification models were trained. An Ensemble Machine Learning (EML) model was obtained by averaging the predictions of models with accuracy on a test set >70 %, with and without patients' clinical characteristics. The EML model combined with clinical data showed an accuracy of 0.76, a sensitivity of 0.88, a specificity of 0.69 with a NPV of 0.90, a PPV of 0.64, with AUC of 0.84. CONCLUSION: NCCT and ML analysis shows promise in predicting FR after complete recanalization following MT in AIS patients. Larger studies are required to confirm these preliminary results.

Compressed SENSitivity Encoding (SENSE): Qualitative and Quantitative Analysis.

BACKGROUND: This study aimed to qualitatively and quantitatively evaluate T1-TSE, T2-TSE and 3D FLAIR sequences obtained with and without Compressed-SENSE technique by assessing the contrast (C), the contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR). METHODS: A total of 142 MRI images were acquired: 69 with Compressed-SENSE and 73 without Compressed-SENSE. All the MRI images were contoured, spatially aligned and co-registered using 3D Slicer Software. Two radiologists manually drew 12 regions of interests on three different structures of CNS: white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). RESULTS: C values were significantly higher in Compressed-SENSE T1-TSE compared to No Compressed-SENSE T1-TSE for three different structures of the CNS. C values were also significantly lower for Compressed-SENSE 3D FLAIR and Compressed-SENSE T2-TSE compared to the corresponding No Compressed-SENSE scans. While CNR values did not significantly differ in GM-WM between Compressed-SENSE and No Compressed-SENSE for the 3D FLAIR and T1-TSE sequences, the differences in GM-CSF and WM-CSF were always statistically significant. CONCLUSION: Compressed-SENSE for 3D T2 FLAIR, T1w and T2w sequences enables faster MRI acquisition, reducing scan time and maintaining equivalent image quality. Compressed-SENSE is very useful in specific medical conditions where lower SAR levels are required without sacrificing the acquisition of helpful diagnostic sequences.

Imaging findings of a case of peliosis hepatis mimicking malignancies.

Peliosis hepatis (PH) is a rare benign pathological entity characterised by dilatation of the hepatic sinusoids. It has been reported to be associated with infection or malignancy, but the aetiology of PH remains unknown. Distinguishing PH from other malignancies can be difficult on imaging studies. This case report describes the incidental finding of PH in a patient undergoing a cardiac computed tomography (CT) scan at our institution. The CT scan incidentally revealed areas of altered density in the liver on the abdominal scans, requiring detailed liver diagnostic studies for better characterisation.

Cerebritis, optic ischemia, and cavernous sinus thrombosis arising from sinonasal mucormycosis.

Brain and ocular infections can be the worst and fatal consequences of sinonasal infections in immunomodulated or immunocompromised patients. We report a case of a 35-year-old female who received an allogenic hematopoietic stem cell transplantation for acute myeloid leukemia, suffering from maxillo-spheno-ethmoidal rhinosinusitis which was complicated by cavernous sinus thrombosis, orbital cellulitis, optic ischemia and cerebritis.

Outcomes and safety of endovascular treatment from 6 to 24 hours in patients with a pre-stroke moderate disability (mRS 3): a multicenter retrospective study.

BACKGROUND: Approximately 30% of patients presenting with acute ischemic stroke (AIS) due to large vessel occlusion have pre-stroke modified Rankin Scale (mRS) scores ≥2. We aimed to investigate the safety and outcomes of endovascular treatment (EVT) in patients with AIS with moderate pre-stroke disability (mRS score 3) in an extended time frame (ie, 6-24 hours from the last time known well). METHODS: Data were collected from five centers in Europe and the USA from January 2018 to January 2023 and included 180 patients who underwent EVT in an extended time frame. Patients were divided into two groups of 90 each (Group 1: pre-mRS 0-2; Group 2: pre-mRS 3; 71% women, mean age 80.3±11.9 years). Primary outcomes were: (1) 3-month good clinical outcome (Group 1: mRS 0-2, Group 2: mRS 0-3) and ΔmRS; (2) any hemorrhagic transformation (HT); and (3) symptomatic HT. Secondary outcomes were successful and complete recanalization after EVT and 3-month mortality. RESULTS: No between-group differences were found in the 3-month good clinical outcome (26.6% vs 25.5%, P=0.974), any HT (26.6% vs 22%, P=0.733), and symptomatic HT (8.9 vs 4.4%, P=0.232). Unexpectedly, ΔmRS was significantly smaller in Group 2 compared with Group 1 (1.64±1.61 vs 2.97±1.69, P<0.001). No between-group differences were found in secondary outcomes. CONCLUSION: Patients with pre-stroke mRS 3 are likely to have similar outcomes after EVT in the extended time frame to those with pre-stroke mRS 0-2, with no difference in safety.

Efficacy of retrograde revascularization in diabetic patients with chronic limb-threatening ischemia after a failed antegrade approach.

BACKGROUND: Chronic limb-threatening ischemia is the end stage of peripheral arterial disease. The revascularization of patients suffering from diabetes mellitus who present chronic total occlusions of below-the-knee vessels can be technically very difficult and sometimes impossible to achieve by performing only an antegrade approach. As regards retrograde recanalization, several studies have investigated the efficacy and safety of this technique in the femoropopliteal axis or in the infrageniculate arterial vessels in patients with advanced atherosclerotic disease. Currently in the literature there are still few studies analyzing the effectiveness of the retrograde approach in the treatment of occlusions of below-the-knee vessels in patients suffering from diabetes mellitus. OBJECTIVES: The purpose of the study was to retrospectively evaluate safety, technical success, and clinical outcome of retrograde transpedal/transtibial recanalization in patients suffering from diabetes mellitus. RESEARCH DESIGN: This is a retrospective observational monocentric study. SUBJECTS: We retrospectively analyzed data over a three-year period (August 2019-September 2022) of patients that underwent revascularization of one or more below-the-knee vessels for chronic limb-threatening ischemia and had a retrograde transpedal/transtibial approach after a failed antegrade transfemoral revascularization. We identified and included in the study 28 out of 352 patients. MEASURES: We evaluated clinical comorbidities, Rutherford-Becker classification, Texas classification, and the occluded vessels (only below-the-knee or multi-level occlusions); we then analyzed technical, procedural and clinical success, survival rate, and procedural complications. All patients included in the study underwent a 6 months follow-up. RESULTS: Patients belonged to Rutherford-Becker stage V (18) or VI (10), Texas wound classification IIC: 7 IID: 8 IIIC: 4 IIID: 9, all suffering from diabetes, and five were on dialysis. Treatment of a femoropopliteal lesion was performed during the same procedure in 6 of 28 patients (28.6%). Technical success was obtained in 25 out of 28 patients (89.3%), and procedural success was achieved in 23 of 28 patients (82.1%). No complications occurred at the pedal/tibial access. One minor complication at the femoral access was observed. The cure rate 6 months after the procedure was 57.1% (16/28 patients), and the 6-month survival rate was 96.4%. Three major amputations (10.7%) and four minor amputations (14.2%) were performed after revascularization procedures. Two patients were readmitted for vascular causes (7.1%). CONCLUSIONS: Retrograde approach for revascularization of below-the-knee vessels in diabetic patients is safe and effective with high procedural and clinical success rates in the absence of significant complications. It should be considered when revascularization cannot be achieved with an antegrade transfemoral approach.

Peritoneal Carcinomatosis of Malignant Gynecological Origin: A Systematic Review of Imaging Assessment.

This systematic review, conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, aims to comprehensively assess the current state of the art of imaging modalities for the evaluation of peritoneal carcinomatosis arising from malignant gynecological origins, with a focus on ovarian and endometrial cancers. A systematic search of relevant databases was performed, adhering to predetermined inclusion and exclusion criteria. Studies reporting the use of computed tomography (CT), magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG) positron emission tomography (PET), PET/CT, and PET/MRI in the assessment of peritoneal carcinomatosis from gynecological malignancies were included. The review encompasses an overview of selected studies, highlighting the strengths and limitations of each imaging modality in diagnosing and characterizing peritoneal carcinomatosis. Overall, a wide variability in the reported accuracy of different imaging techniques emerges from literature, mainly due to the type of the study, technical issues, and patient characteristics. Although a meta-analysis could not be performed due to a scarcity of data, this systematic review provides valuable insights into the several imaging approaches used in peritoneal carcinomatosis of gynecological origin. The findings aim to inform clinical decision making and guide future research endeavors in this critical aspect of gynecological oncology.

Midterm follow-up after embolization of intracranial aneurysms proximal to the circle of Willis with the Silk Vista flow diverter: the I-MAMA registry.

PURPOSE: The aim of this registry was to assess technical success, procedural safety and mid- to long-term follow-up results of the Silk Vista "Mama" (SVM) flow diverter (BALT, Montmorency, France) for the treatment of proximal intracranial aneurysms. METHODS: Between August 2020 and March 2022, data from nine Italian neurovascular centres were collected. Data included patients' clinical presentation, aneurysms' size, location and status, technical details, overall complications and mid- to long-term angiographic follow-up. RESULTS: Forty-eight aneurysms in 48 patients were treated using the SVM. Most aneurysms were small (≤ 10 mm: no. 29, 60%) and unruptured (no. 31, 65%); 13 aneurysms were recurrent after coiling or clipping. 37/48 aneurysms involved the internal carotid artery (77%). Optimal opening and complete wall apposition of the device were achieved in 46 out of 48 cases (96%). Four intra- or periprocedural complications occurred (two thrombotic complications successfully resolved, one cerebellar ischemia, one perirenal hematoma), without new neurological deficit. No significant intra-stent stenosis or stent displacement was observed during follow-up. No FD-related morbidity nor mortality was reported. At midterm (6-12 months) to long-term (> 12 months) follow-up, complete aneurysm occlusion (OKM D) was achieved in 76% of cases. Eighty-eight percent of patients had complete aneurysm occlusion or entry remnant (OKM D + C). CONCLUSIONS: Our experience suggests that the new generation of low-profile SVM flow diverter for the treatment of proximal intracranial aneurysms is safe and effective, with low rates of intraprocedural complications and acceptable mid- to long-term occlusion rate.

The role of cardiac computed tomography in diagnostic and prognostic assessment of pregnancy related spontaneous coronary artery dissection: a case report.

Spontaneous coronary artery dissection (SCAD) is the most common cause of myocardial infarction during pregnancy or the postpartum period and has a major impact on cardiovascular morbidity and death in pregnant women. A 38-year-old woman with sudden cardiac arrest ten days postpartum urgently underwent coronarography, which showed an intraparietal hematoma of the left anterior descending (LAD) artery. Two days later, coronary computed tomography angiography (CCTA) was performed, which showed the evidence of SCAD in the mid-distal tract of LAD and the presence of transmural ischemic infarction in the apex and mid antero-septal wall in delayed acquisition. The patient was treated with a beta-blocker. Four months later CCTA showed complete resolution of SCAD and evolution of the infarcted areas. Given the high accuracy and noninvasiveness of CCTA, our case highlights the potential role of this imaging modality in the diagnosis and follow-up of pregnancy associated SCAD.

Transperineal Laser Ablation (TPLA) Treatment of Focal Low-Intermediate Risk Prostate Cancer.

Background: This interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low-intermediate-risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). Methods: Forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low-to-intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a Day Hospital setting under local anesthesia. Patients underwent regular clinical and functional assessments through the international index of erectile function (IIEF-5) and the International Prostatism Symptom Score (IPSS), PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. Statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. Results: Forty patients were initially included, with fifteen lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. Biopsies at 36 months revealed no malignant findings in 20 patients. No deterioration in sexual function or urinary symptoms was recorded. Conclusions: FLA appears to be safe, feasible, and effective in the index lesion treatment of low-intermediate-risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life.

CT Images in Follicular Lymphoma: Changes after Treatment Are Predictive of Cardiac Toxicity in Patients Treated with Anthracycline-Based or R-B Regimens.

The aim of this study is to evaluate changes in epicardial adipose tissue (EAT) and cardiac extracellular volume (ECV) in patients with follicular lymphoma (FL) treated with R-CHOP-like regimens or R-bendamustine. We included 80 patients with FL between the ages of 60 and 80 and, using computed tomography (CT) performed at onset and at the end of treatment, we assessed changes in EAT by measuring tissue density at the level of the cardiac apex, anterior interventricular sulcus and posterior interventricular sulcus of the heart. EAT is known to be associated with metabolic syndrome, increased calcium in the coronary arteries and therefore increased risk of coronary artery disease. We also evaluated changes in ECV, which can be used as an early imaging marker of cardiac fibrosis and thus myocardial damage. The R-CHOP-like regimen was associated with lower EAT values (p < 0.001), indicative of a less active metabolism and more adipose tissue, and an increase in ECV (p < 0.001). Furthermore, in patients treated with anthracyclines and steroids (R-CHOP-like) there is a greater decrease in ejection fraction (EF p < 0.001) than in the R-B group. EAT and ECV may represent early biomarkers of cardiological damage, and this may be considered, to our knowledge, the first study investigating radiological and cardiological parameters in patients with FL.

Low-Dose Occupational Exposure to Ionizing Radiation and Cardiovascular Effects: A Narrative Review.

Historically, non-cancer diseases have not been considered a health risk following low-dose exposure to ionizing radiation. However, it is now well known that high-dose ionizing radiation causes cardiovascular disease, and emerging epidemiological evidence suggests an excess risk of non-cancer diseases even following exposure to lower doses of ionizing radiation than previously thought. In fact, the evidence is strongest for cardiovascular disease (CVD). The aim of this review was to report the most representative studies and data on the risk of CVD from low-dose radiation in people with occupational exposure. We reported the results of 27 articles selected from a database search of 1151 studies. The results show a complex evidence landscape on the relationship between radiation exposure and cardiovascular disease. In general, published papers show a positive association between ionizing radiation exposure and dermal microcirculation damage, ischemic heart disease, and cerebrovascular disease. Overall, they highlight the need for comprehensive and detailed research to clarify this relationship. Due to limited statistical power, the dose-risk relationship below 0.5 Gy is inconclusive, but if this relationship is found to have no threshold, it could have a significant impact on current estimates of health risks at low doses.

One Fell Swoop: Septic Muscle Embolism and Central Venous Catheter Infection Imaged with [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

We describe the case of a 43-year-old female with hereditary hemochromatosis, previously without cardiac issues, who presented with a severe fever (>40 to 41 °C) to our hospital. Initial assessments, including transthoracic echocardiography, showed no typical signs of infective endocarditis. A contrast-enhanced CT scan revealed a hypodense area in the right subscapular muscle, alongside pleural thicknesses. Due to the critical condition, a central venous catheter (CVC) was implanted for immediate intravenous treatment. Subsequent blood cultures, positive for Staphylococcus aureus, and transesophageal echocardiography led to a diagnosis of multivalvular infective endocarditis (MIE). Subsequently, the patient underwent positron emission tomography/computed tomography (PET/CT) with [18F]Fluorodeoxyglucose ([18F]FDG), which detected increased tracer incorporation in the muscle lesion, CVC, and pleural thicknesses. The final diagnosis was CVC infection and septic embolism to the subscapular muscle in a patient with pleuritis. This case showcases the critical role of [18F]FDG PET/CT as whole-body imaging modality in diagnosing and managing complex infective cases.

Colo-colic intussusception in an adult caused by lipoma: Case report of a rare condition.

This report describes the case of a 56-year-old woman who presented at the emergency room with a 3-week history of severe, intermittent abdominal pain. A CT scan revealed colo-colic intussusception caused by a large, substenosing mass with predominant adipose density. Subsequent endoscopic examination with biopsy revealed a necrotic tissue covering the mass, without definitive histological characterization. A second biopsy led to the extremely rare diagnosis of colo-colic lipoma. While intussusception is rare in adults, it's important to consider it as a differential diagnosis, especially when presenting with abdominal pain and signs of bowel obstruction. Timely diagnosis and appropriate treatment are essential to prevent complications.

Influence of scan duration on dynamic contrast -enhanced magnetic resonance imaging pharmacokinetic parameters for brain lesions.

OBJECTIVE: Gadolinium-based contrast agent needs time to leak into the extravascular-extracellular space, leak back into the vascular space, and reach an equilibrium state. For this reason, acquisition times of <10 min may cause inaccurate estimation of pharmacokinetic parameters. Since no studies have been conducted on the influence of long scan times on DCE-MRI parameters in brain tumors, the aim of this study is to investigate the variation of DCE-MRI-derived kinetic parameters as a function of acquisition time, from 5 to 10 min in brain tumors. MATERIALS AND METHODS: Fifty-two patients with histologically confirmed brain tumors were enrolled in this retrospective study, and examination at 3 T, DCE-MRI, with scan duration of 10 min, was used for retrospective generation of 6 sets of quantitative DCE-MRI maps (Ktrans, Ve and Kep) from 5 to 10 min. Features were extracted from the DCE-MRI maps in contrast enhancement (CE) volumes. Kruskal-Wallis with post-hoc correction and coefficient of variation (CoV) were used as statistical test to compare DCE-MRI maps obtained from 6 data sets. SIGNIFICANCE: p < 0.05. RESULTS: No differences in Ktrans features in CE volumes between different scan durations. Ve, Kep features in CE volumes were influenced by different data length. The highest number of significantly different Ve and Kep features in CE volumes were between 5 min and 10 min (p < 0.013), 5 min and 9 min (p < 0.044), 6 min and 10 min (p < 0.040). CoV of Kep was reduced from 5 min to 10 min, going from highly variable (CoV = 0.70) to mildly variable (CoV = 0.42). CONCLUSION: Kep and Ve were time-dependent in brain tumors, so a longer scan time is needed to obtain reliable parameter values. Ktrans was found to be time-independent, as it remains the same in all 6 acquisition times and is the only reliable parameter with short acquisition times.

Clinical and functional characterization of COL2A1 p.Gly444Ser variant: From a fetal phenotype to a previously undisclosed postnatal phenotype.

COL2A1 gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.5:c.1330G>A;p.Gly444Ser variant detected in the COL2A1 gene through trio-based prenatal exome sequencing in a fetus presenting a severe skeletal phenotype at 31 Gestational Weeks and in his previously undisclosed mild-affected father. Functional studies on father's cutaneous fibroblasts, along with in silico protein modeling and in vitro chondrocytes differentiation, showed intracellular accumulation of collagen-II, its localization in external Golgi vesicles and nuclear morphological alterations. Extracellular matrix showed a disorganized fibronectin network. These results showed that p.Gly444Ser variant alters procollagen molecules processing and the assembly of mature type-II collagen fibrils, according to COL2A1-chain disorganization, displayed by protein modeling. Clinical assessment at 38 y.o., through a reverse-phenotyping approach, revealed limp gait, short and stocky appearance. X-Ray and MRI showed pelvis asymmetry with severe morpho-structural alterations of the femoral heads bilaterally, consistent with a mild form of type-II collagenopathy. This study shows how the fusion of genomics and clinical expertise can drive a diagnosis supported by cellular and bioinformatics studies to effectively establish variants pathogenicity.

Transperineal laser ablation (TPLA) with ultrasound/MRI fusion guidance in the treatment of localized radiotherapy-resistant prostate cancer.

Objective: The objective of this study was to assess the technical feasibility, safety, and efficacy of transperineal laser ablation (TPLA) guided by ultrasound/magnetic resonance (MR) fusion as a salvage treatment for refractory focal prostate cancer. Methods: A total of five patients who had undergone radiation therapy (RT) for prostate carcinoma and biochemical recurrence, confirmed by both prostate-specific antigen (PSA) levels and MRI (3T mpMRI), were enrolled in this study. Focal ablation was performed using a 1064 nm diode laser. Post-ablation follow-up was conducted for a duration of 18 months, which included regular PSA sampling, 3T mpMRI, and ultrasound/MR fusion-guided biopsies systematic and targeted at the site of the focal treatment. Results: The focal ablation procedure was carried out in an outpatient setting regimen with optimal clinical and biochemical outcomes. No recurrence was detected throughout the follow-up period. Conclusion: TPLA focal treatment effectively manages local recurrences of RT refractory prostate cancer without side-effects or complications. Preservation of quality of life and functional outcomes, along with a >70% reduction in PSA, were achieved. Advances in knowledge: Our study investigated TPLA as a salvage treatment for low-risk recurrent prostate cancer after RT, demonstrating its tolerability, feasibility, and effectiveness.

MRI and Clinical Biomarkers Overlap between Glaucoma and Alzheimer's Disease.

Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy between signs and symptoms and underlie the analogy of this disease with neurodegenerative dementias, such as Alzheimer's disease, and with the complex group of pathologies commonly referred to as "disconnection syndromes." This review aims to summarize the current state of the art on the use of advanced neuroimaging techniques in glaucoma and Alzheimer's disease, highlighting the emerging biomarkers shared by both diseases.

Untailored vs. Gender- and Body-Mass-Index-Tailored Skeletal Muscle Mass Index (SMI) to Assess Sarcopenia in Advanced Head and Neck Squamous Cell Carcinoma (HNSCC).

(1) Background: Sarcopenia lasting >1 year might be considered a chronic condition in many HNSCC patients. CT-scan-derived Skeletal Muscle Mass Index (SMI) is an established surrogate of sarcopenia; yet, the cut-off reported in the literature (literature-based, lb-SMI < 43.2) is mainly based on the risk of chemoradiotherapy-induced toxicity, and the optimal value to discriminate OS is under-investigated. (2) Methods: The effect on OS of the lb-SMI cutoff was compared with an untailored OS-oriented SMI cutoff obtained in a cohort of consecutive advanced HNSCC patients treated with primary chemoradiotherapy, bio-chemotherapy or chemo-immunotherapy (cohort-specific, cs-SMI cutoff). Gender- and BMI-tailored (gt-SMI and bt-SMI) cut-offs were also evaluated. Cutoff values were identified by using the maximally selected rank statistics for OS. (3) Results: In 115 HNSCC patients, the cs-SMI cutoff was 31.50, which was lower compared to the lb-SMI reported cut-off. The optimal cut-off separately determined in females, males, overweight and non-overweight patients were 46.02, 34.37, 27.32 and 34.73, respectively. gt-SMI categorization had the highest effect on survival (p < 0.0001); its prognostic value was independent of the treatment setting or the primary location and was retained in a multivariate cox-regression analysis for OS including other HNSCC-specific prognostic factors (p = 0.0004). (4) Conclusions: A tailored SMI assessment would improve clinical management of sarcopenia in chemoradiotherapy-, bio-chemotherapy- or chemo-immunotherapy-treated HNSCC patients. Gender-based SMI could be used for prognostication in HNSCC patients.