First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE­048.

BACKGROUND: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. METHODS: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. RESULTS: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. CONCLUSION: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. CLINICAL TRIAL REGISTRATION: NCT02358031.

Distance-dependent neuromodulation effect during thermal ablation for atrial fibrillation.

INTRODUCTION: Thermal atrial fibrillation (AF) ablation exerts an additive treatment effect on the cardiac autonomic nervous system (CANS). This effect is mainly reported during ablation of the right superior pulmonary vein (RSPV), modulating the right anterior ganglionated plexus (RAGP), which contains parasympathetic innervation to the sinoatrial node in the epicardial fat pad between RSPV and superior vena cava (SVC). However, a variable response to neuromodulation after ablation is observed, with little to no effect in some patients. Our objective was to assess clinical and anatomic predictors of thermal ablation-induced CANS changes, as assessed via variations in heart rate (HR) postablation. METHODS: Consecutive paroxysmal AF patients undergoing first-time PV isolation by the cryoballoon (CB) or radiofrequency balloon (RFB) within a 12-month time frame and with preprocedural cardiac computed tomography (CT), were evaluated. Preablation and 24-h postablation electrocardiograms in sinus rhythm were collected and analyzed to assess HR. Anatomic evaluation by CT included the measurement of the shortest distance between the SVC and RSPV ostium (RSPV-SVC distance). RESULTS: A total of 97 patients (CB, n = 50 vs. RFB, n = 47) were included, with similar baseline characteristics between both groups. A significant HR increase postablation (ΔHR ≥ 15 bpm) occurred in a total of 37 patients (38.1%), without difference in number of patients between both thermal ablation technologies (CB, 19 [51%]), RFB, 18 [49%]). Independent predictors for increased HR were RSPV-SVC distance (odds ratio [OR]: 0.49, CI: 0.34-0.71, p value < .001), and age (OR: 0.94, CI: 0.89-0.98, p value = .003). CONCLUSIONS: Thermal balloon-based PV isolation influences the CANS through its effect on the RAGP, especially in younger patients and patients with shorter RSPV-SVC distance.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Prediction of prognosis in lung cancer using machine learning with inter-institutional generalizability: A multicenter cohort study (WJOG15121L: REAL-WIND).

OBJECTIVES: Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis. MATERIALS AND METHODS: This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities. RESULTS: Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9-17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88-0.91), 0.85 (0.84-0.87), 0.83 (0.81-0.85), and 0.85 (0.82-0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84-0.92), 0.84 (0.78-0.88), 0.84 (0.76-0.89), and 0.84 (0.75-0.90) at 180, 360, 720, and 1,080 days, respectively. CONCLUSION: This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings.

Impact of Advanced Extravascular Calcified Plaque on the Assessment of Coronary Stenosis Severity.

Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) provide high diagnostic accuracy for coronary artery disease (CAD), consistent with invasive coronary angiography (ICA), the gold standard diagnostic technique. The presence of calcified components, however, complicates the interpretation of coronary stenosis severity. We present a case where there was a discrepant assessment of coronary stenosis severity between CCTA/FFRCT (indicating significant obstructive CAD) and ICA (showing no apparent obstructive CAD). CCTA/FFRCT revealed that the stenotic lesion, located in the middle segment of the left circumflex artery, was surrounded by plaque components. The proximal and distal portions of the stenotic lesion consisted of 80.9% luminal volume, 0.2% low-attenuation plaque, 13.4% intermediate-attenuation plaque, and 5.5% calcified plaque. In contrast, the stenotic lesion itself contained 50.0% luminal volume, 0.3% low-attenuation plaque, 26.7% intermediate-attenuation plaque, and 22.9% calcified plaque. Invasive coronary angiography showed no apparent obstructive CAD, implying that the lesions appearing as significant obstructive CAD on CCTA/FFRCT were likely overestimated due to the effects of extravascular calcified plaque. Advanced extravascular calcified plaque surrounding the lesion may cause several artifacts (such as blooming and/or beam hardening artifacts) and/or vasodilator dysfunction (either organic and/or functional), potentially leading to an overestimation of the severity of coronary stenosis in CCTA/FFRCT assessments.

Cardiac computed tomography-derived coronary artery volume to myocardial mass in patients with severe coronary artery disease.

BACKGROUND: Coronary artery lumen volume (V) to myocardial mass (M) ratio (V/M) can show the mismatch between epicardial coronary arteries and the underlying myocardium. METHODS: The V, M and V/M were obtained from the coronary computed tomography angiography (CCTA) of patients in the FAST-TRACK CABG study, the first-in-human trial of coronary artery bypass grafting (CABG) guided solely by CCTA and fractional flow reserve derived from CCTA (FFRCT) in patients with complex coronary artery disease (CAD). The correlations between V/M ratios and baseline characteristics were determined and compared with those from the ADVANCE registry, an unselected cohort of historical controls with chronic CAD. RESULTS: The V/M ratio was obtained in 106 of the 114 pre-CABG CCTAs. Mean age was 65.6 years and 87% of them were male. The anatomical SYNTAX score from CCTA was significantly higher than the functional SYNTAX score derived using FFRCT [43.1 (15.2) vs 41.1 (16.5), p â€‹< â€‹0.001]. Mean V, M, and V/M were 2204 â€‹mm3, 137 â€‹g, and 16.5 â€‹mm3/g, respectively. There were weak negative correlations between V and anatomical and functional SYNTAX scores (Pearson's r â€‹= â€‹-0.26 and -0.34). V and V/M had a strong correlation (r â€‹= â€‹0.82). The V/M ratio in the current study was significantly lower than that in the ADVANCE registry (median 16.1 vs. 24.8 [1st quartile 20.1]). CONCLUSION: Systematically smaller V/M ratios were found in this population with severe CAD requiring CABG compared to an unselected cohort with chronic CAD. The V/M ratio could provide additional non-invasive assessment of CAD especially when combined with FFRCT.

Managing Iatrogenic Aortic Dissection: Insight From 3D Holographic Imaging and CT Computational Fluid Dynamic Simulations.

Iatrogenic aortic dissection is a rare but life-threatening complication of coronary artery bypass surgery. We report a case with incidentally detected iatrogenic aortic dissection related to aorta cross-clamping that was successfully managed with watchful follow-up. The decision making was based on 3-dimensional holographic and fluid dynamic analysis guidance.

Quantitative coronary computed tomography assessment for differentiating between total occlusions and severe stenoses.

BACKGROUNDS: The impact of quantitative assessment to differentiate total occlusions (TOs) from severe stenoses on coronary computed tomography angiography (CCTA) remains unknown. OBJECTIVE: This study investigated whether quantitative characteristics assessed on CCTA could help differentiate a TO from a severe stenosis on invasive coronary angiography (ICA). METHODS: This study is a sub-analysis of the FASTTRACK CABG (NCT04142021) in which both CCTA and ICA were routinely performed. Quantitative analysis was performed with semi-automated CCTA plaque-analysis software. Blinded analysts compared TOs on CCTA, defined as a complete lack of contrast opacification within the coronary occlusion, with corresponding ICA. RESULTS: Eighty-four TOs were seen on CCTA in 59 of the 114 patients enrolled in the trial. The concordance in diagnosing a TO between ICA and CCTA was 56.0% (n â€‹= â€‹47). Compared to severe stenoses, TOs had a significantly longer lesion length (25.1 â€‹± â€‹23.0 â€‹mm vs 9.4 â€‹± â€‹11.2 â€‹mm, P â€‹< â€‹0.001). The best cut-off value to differentiate a TO from severe stenosis was a lesion length of 5.5 â€‹mm (area under the curve 0.77, 95% CI: 0.66-0.87), with a 91.1% sensitivity and 61.1% specificity. Dense calcium percentage atheroma volume (PAV) was significantly higher in TOs compared to severe stenoses (18.7 â€‹± â€‹19.6% vs. 6.6 â€‹± â€‹13.0%, P â€‹< â€‹0.001), whilst the opposite was seen for fibro-fatty PAV (31.3 â€‹± â€‹14.2% vs. 19.5 â€‹± â€‹10.5%, P â€‹< â€‹0.001). On a multivariable logistic regression analysis, lesion length (>5.5 â€‹mm) was the only parameter associated with differentiating a TO from a severe stenosis. CONCLUSION: In quantitative CCTA analysis, a lesion length >5.5 â€‹mm was the only independent predictor differentiating a TO from a severe stenosis. NCT REGISTRATION NUMBER: NCT04142021.

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

Discrepancy in Diagnosing Coronary Artery Occluded Lesion: CT-Derived Fractional Flow Reserve (FFRCT) Versus Invasive Coronary Angiography.

Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) findings demonstrate high diagnostic accuracy, aligning consistently with invasive coronary angiography (ICA), the gold standard diagnostic technique for coronary artery disease. The differential diagnosis of total versus subtotal coronary occlusion is crucial in determining the appropriate treatment strategy. Subtotal coronary occlusions composed of vulnerable tissue can sometimes present as total coronary occlusions on ICA. This presentation can be inconsistent with findings from CCTA and FFRCT. This case report presents discrepant findings between CCTA, which indicated subtotal coronary occlusion, and ICA, which suggested total coronary occlusion. The stenotic lesion, filled with vulnerable tissue (low-attenuation plaque volume: 20.3 mm3 and intermediate-attenuation plaque volume: 71.6 mm3), could be dilated with a vasodilator during maximal hyperemia. This dilation facilitated the acquisition of CCTA and FFRCT images. We were able to diagnose subtotal coronary occlusion and identify the overall anatomical structure of the vessels prior to percutaneous coronary intervention (PCI). This allowed us to perform a successful and uncomplicated PCI.

Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade.

BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms of the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated patients who received nivolumab. A retrospective observational study was performed for patients treated with any PD-1/PD-L1 blockade therapy (cohorts B and C), cytotoxic chemotherapy (cohort D), or targeted therapy (cohort E). Plasma samples from all patients were assayed for soluble immune-checkpoint molecules with a highly sensitive chemiluminescence-based assay.RESULTSNonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such an association was not apparent for patients treated with cytotoxic chemotherapy or targeted therapy. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the 3 soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of soluble PD-L1 (sPD-L1) and sCTLA-4 efficiently discriminated responsiveness to PD-1/PD-L1 blockade among patients with immune-reactive tumors.CONCLUSIONCombinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest that such a combination better predicts, along with tPD-L1, for the response of patients with NSCLC.TRIAL REGISTRATIONUMIN000019674.FUNDINGThis study was funded by Ono Pharmaceutical Co. Ltd. and Sysmex Corporation.

Feasibility and accuracy of real-time 3D-holographic graft length measurements.

Aims: Mixed reality (MR) holograms can display high-definition images while preserving the user's situational awareness. New MR software can measure 3D objects with gestures and voice commands; however, these measurements have not been validated. We aimed to assess the feasibility and accuracy of using 3D holograms for measuring the length of coronary artery bypass grafts. Methods and results: An independent core lab analyzed follow-up computer tomography coronary angiograms performed 30 days after coronary artery bypass grafting in 30 consecutive cases enrolled in the FASTTRACK CABG trial. Two analysts, blinded to clinical information, performed holographic reconstruction and measurements using the CarnaLife Holo software (Medapp, Krakow, Poland). Inter-observer agreement was assessed in the first 20 cases. Another analyst performed the validation measurements using the CardIQ W8 CT system (GE Healthcare, Milwaukee, Wisconsin). Seventy grafts (30 left internal mammary artery grafts, 31 saphenous vein grafts, and 9 right internal mammary artery grafts) were measured. Holographic measurements were feasible in 97.1% of grafts and took 3 minutes 36 s ± 50.74 s per case. There was an excellent inter-observer agreement [interclass correlation coefficient (ICC) 0.99 (0.97-0.99)]. There was no significant difference between the total graft length on hologram and CT [187.5 mm (157.7-211.4) vs. 183.1 mm (156.8-206.1), P = 0.50], respectively. Hologram and CT measurements are highly correlated (r = 0.97, P < 0.001) with an excellent agreement [ICC 0.98 (0.97-0.99)]. Conclusion: Real-time holographic measurements are feasible, quick, and accurate even for tortuous bypass grafts. This new methodology can empower clinicians to visualize and measure 3D images by themselves and may provide insights for procedural strategy.

Murray law-based quantitative flow ratio to assess left main bifurcation stenosis: selecting the angiographic projection matters.

Murray law-based quantitative flow ratio (µQFR) assesses fractional flow reserve (FFR) in bifurcation lesions using a single angiographic view, enhancing the feasibility of analysis; however, accuracy may be compromised in suboptimal angiographic projections. FFRCT is a well-validated non-invasive method measuring FFR from coronary computed tomographic angiography (CCTA). We evaluated the feasibility of µQFR in left main (LM) bifurcations, the impact of the optimal/suboptimal fluoroscopic view with respect to CCTA, and its diagnostic concordance with FFRCT. In 300 patients with three-vessel disease, the values of FFRCT and µQFR were compared at distal LM, proximal left anterior descending artery (pLAD) and circumflex artery (pLCX). The optimal viewing angle of LM bifurcation was defined on CCTA by 3-dimensional coordinates and converted into a 2-dimensional fluoroscopic view. The best fluoroscopic projection was considered the closest angulation to the optimal viewing angle on CCTA. µQFR was successfully computed in 805 projections. In the best projections, µQFR sensitivity was 88.2% (95% CI 76.1-95.6) and 84.8% (71.1-93.7), and specificity was 96.8% (93.8-98.6) and 97.2% (94.4-98.9), in pLAD and pLCX, respectively, with regard to FFRCT. The AUC of µQFR for predicting FFRCT ≤ 0.80 tended to be improved using the best versus suboptimal projections (0.94 vs. 0.89 [p = 0.048] in pLAD; 0.94 vs. 0.88 [p = 0.075] in pLCX). Computation of µQFR in LM bifurcations using a single angiographic view showed high feasibility from post-hoc analysis of coronary angiograms obtained for clinical purposes. The fluoroscopic viewing angle influences the diagnostic performance of physiological assessment using a single angiographic view.

Impact of vessel morphology on CT-derived fractional-flow-reserve in non-obstructive coronary artery disease in right coronary artery.

OBJECTIVES: Computed tomography (CT)-derived fractional flow reserve (FFRCT) decreases continuously from proximal to distal segments of the vessel due to the influence of various factors even in non-obstructive coronary artery disease (NOCAD). It is known that FFRCT is dependent on vessel-length, but the relationship with other vessel morphologies remains to be explained. PURPOSE: To investigate morphological aspects of the vessels that influence FFRCT in NOCAD in the right coronary artery (RCA). METHODS: A total of 443 patients who underwent both FFRCT and invasive coronary angiography, with < 50% RCA stenosis, were evaluated. Enrolled RCA vessels were classified into two groups according to distal FFRCT: FFRCT ≤ 0.80 (n = 60) and FFRCT > 0.80 (n = 383). Vessel morphology (vessel length, lumen diameter, lumen volume, and plaque volume) and left-ventricular mass were assessed. The ratio of lumen volume and vessel length was defined as V/L ratio. RESULTS: Whereas vessel-length was almost the same between FFRCT ≤ 0.80 and > 0.80, lumen volume and V/L ratio were significantly lower in FFRCT ≤ 0.80. Distal FFRCT correlated with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). Among all vessel-related parameters, V/L ratio showed the highest correlation with distal FFRCT (r = 0.61, p < 0.0001). Multivariable analysis showed that calcified plaque volume was the strongest predictor of distal FFRCT, followed by V/L ratio (ß-coefficient = 0.48, p = 0.03). V/L ratio was the strongest predictor of a distal FFRCT ≤ 0.80 (cut-off 8.1 mm3/mm, AUC 0.88, sensitivity 90.0%, specificity 76.7%, 95% CI 0.84-0.93, p < 0.0001). CONCLUSIONS: Our study suggests that V/L ratio can be a measure to predict subclinical coronary perfusion disturbance. CLINICAL RELEVANCE STATEMENT: A novel marker of the ratio of lumen volume to vessel length (V/L ratio) is the strongest predictor of a distal CT-derived fractional flow reserve (FFRCT) and may have the potential to improve the diagnostic accuracy of FFRCT. KEY POINTS: • Physiological FFRCT decline depends not only on vessel length but also on the lumen volume in non-obstructive coronary artery disease in the right coronary artery. • FFRCT correlates with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). • Of vessel-related parameters, V/L ratio is the strongest predictor of a distal FFRCT and an optimal cut-off value of 8.1 mm3/mm.

Clinical and prognostic incremental value of FFRCT in screening of patients with obstructive coronary artery disease.

BACKGROUND: Coronary computed tomography angiography (CCTA) -derived fractional flow reserve (FFRCT) is recommended to evaluate the functional consequences of obstructive coronary artery disease (OCAD). Real-world incremental impacts of FFRCT use still remains under debate. METHODS: 1601 patients with suspected OCAD on CCTA (>50 â€‹% stenosis), including 808 (50.5 â€‹%) patients evaluated by FFRCT, were included from a 2013-2021 registry. Propensity adjusted impacts of FFRCT use on rates of invasive coronary angiography (ICA), myocardial revascularization (MR) and post MR major adverse cardiac events (MACE) were reported, including a sensitivity analysis in severe OCAD (>70 â€‹% stenosis) (n â€‹= â€‹450). Accuracy of numerical and comprehensive FFRCT interpretations in selection of patients requiring a MR were also compared. RESULTS: 1160 (72,5 â€‹%) ICA, 559 (34.9 â€‹%) MR and 137 (24.5 â€‹%) post MR MACE occurred at 4.7 â€‹± â€‹1.9 years. FFRCT use was independently associated with decreased rate of ICA and MR (OR: 0.66; 95 â€‹% CI 0.53-0.83, p â€‹< â€‹0.001 and OR: 0.71; 95 â€‹% CI 0.58-0.88, p â€‹< â€‹0.01, respectively). Compared to the numerical interpretation, the FFRCT comprehensive assessment increased the ratio of MR per ICA (61.7 â€‹% vs 50.1 â€‹%, p â€‹< â€‹0.01) and was more accurate in selection of patients requiring MR. FFRCT reduced post MR MACE (OR: 0.64; 95 â€‹% CI 0.43-0.96, p â€‹< â€‹0.05). All these associations were no longer observed in severe OCAD. CONCLUSION: Implementing FFRCT in OCAD patients reduces ICA use, improves selection of patients requiring MR and reduces post MR MACE. However, these incremental values of FFRCT were no longer observed in severe OCAD.

Coronary artery disease in atrial fibrillation ablation: impact on arrhythmic outcomes.

AIMS: Catheter ablation (CA) is an established treatment for atrial fibrillation (AF). A computed tomography (CT) may be performed before ablation to evaluate the anatomy of pulmonary veins. The aim of this study is to investigate the prevalence of patients with coronary artery disease (CAD) detected by cardiac CT scan pre-ablation and to evaluate the impact of CAD and revascularization on outcomes after AF ablation. METHODS AND RESULTS: All consecutive patients with AF diagnosis, hospitalized at Universitair Ziekenhuis Brussel, Belgium, between 2015 and 2019, were prospectively screened for enrolment in the study. Inclusion criteria were (i) AF diagnosis, (ii) first procedure of AF ablation with cryoballoon CA, and (iii) contrast CT scan performed pre-ablation. A total of 576 consecutive patients were prospectively included and analysed in this study. At CT scan, 122 patients (21.2%) were diagnosed with CAD, of whom 41 patients (7.1%) with critical CAD. At survival analysis, critical CAD at CT scan was a predictor of atrial tachyarrhythmia (AT) recurrence during the follow-up, only in Cox univariate analysis [hazard ratio (HR) = 1.79] but was not an independent predictor in Cox multivariate analysis. At Cox multivariate analysis, independent predictors of AT recurrence were as follows: persistent AF (HR = 2.93) and left atrium volume index (HR = 1.04). CONCLUSION: In patients undergoing CT scan before AF ablation, critical CAD was diagnosed in 7.1% of patients. Coronary artery disease and revascularization were not independent predictors of recurrence; thus, in this patient population, AF ablation should not be denied and can be performed together with CAD treatment.

The combination of soluble forms of PD-1 and PD-L1 as a predictive marker of PD-1 blockade in patients with advanced cancers: a multicenter retrospective study.

Introduction: The clinical relevance of soluble forms of programmed cell death-1 (sPD-1) and programmed cell death-ligand 1 (sPD-L1) remains unclear. We here investigated the relation between the efficacy of PD-1 blockade and pretreatment plasma levels of sPD-1 and sPD-L1 across a broad range of cancer types. Methods: We retrospectively analyzed clinical data from 171 patients with advanced solid tumors who received nivolumab or pembrolizumab monotherapy regardless of treatment line. The concentrations of sPD-1 and sPD-L1 were measured with a fully automated immunoassay (HISCL system). Results: The study subjects comprised patients with head and neck cancer (n = 50), urothelial cancer (n = 42), renal cell cancer (n = 37), gastric cancer (n = 20), esophageal cancer (n = 10), malignant pleural mesothelioma (n = 6), or microsatellite instability-high tumors (n = 6). High or low levels of sPD-1 or sPD-L1 were not significantly associated with progression-free survival (PFS) or overall survival (OS) for PD-1 blockade in the entire study population. Comparison of treatment outcomes according to combinations of high or low sPD-1 and sPD-L1 levels, however, revealed that patients with low sPD-1 and high sPD-L1 concentrations had a significantly poorer PFS (HR of 1.79 [95% CI, 1.13-2.83], p = 0.01) and a tendency toward poorer OS (HR of 1.70 [95% CI, 0.99-2.91], p = 0.05) compared with all other patients. Conclusion: Our findings suggest that the combination of low sPD-1 and high sPD-L1 levels is a potential negative biomarker for PD-1 blockade therapy.

CCTA-based CABG SYNTAX Score: a tool to evaluate completeness of coronary segment revascularization after bypass surgery.

To describe the updated coronary computed tomographic angiography (CCTA)-based coronary artery bypass graft (CABG) anatomic SYNTAX Score (aSS) and assess its utility and reproducibility for assessing the completeness of revascularization after CABG. The CCTA-CABG aSS is a visual assessment using CCTA post-CABG which quantifies the failure in effectively grafting stenotic coronary segments, and therefore assesses the completeness of surgical revascularization. It is calculated by subtracting the aSS of successfully anastomosed coronary segments from the aSS of the native coronary tree. The inter-observer reproducibility of the CCTA-CABG aSS was evaluated in 45 consecutive patients with three-vessel disease with or without left main disease who underwent a CCTA 30 days (± 7 days) after CABG. The CCTA-CABG aSS was evaluated in 45 consecutive patients with 117 bypass grafts and 152 anastomoses. The median native coronary aSS was 35.0 [interquartile range (IQR) 27.0-41.0], whilst the median CCTA-CABG aSS was 13.0 (IQR 9.0-20.5). The inter-observer level of agreement for the native coronary aSS and the CCTA-CABG aSS were both substantial with respective Kappas of 0.67 and 0.61. The CCTA-CABG aSS was feasible in all patients who underwent CABG for complex coronary artery disease with substantial inter-observer reproducibility, and therefore can be used to quantify the completeness of revascularization after CABG.

Clinical outcomes and failure patterns after postoperative radiotherapy for oral cavity squamous cell carcinoma.

PURPOSE: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). METHODS: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50-66) administered in 30 fractions (range 25-33). RESULTS: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC.