Prognostic Information Research Articles

In vivo mapping of cellular resolution neuropathology in brain ischemia with diffusion MRI.

Noninvasive mapping of cellular pathology can provide critical diagnostic and prognostic information. Recent advances in diffusion magnetic resonance imaging enabled in vivo examination of tissue microstructures well beyond the imaging resolution. Here, we proposed to use diffusion time-dependent diffusion kurtosis imaging (tDKI) to simultaneously assess cellular morphology and transmembrane permeability in hypoxic-ischemic (HI) brain injury. Through numerical simulations and organoid imaging, we demonstrated the feasibility of capturing effective size and permeability changes using tDKI. In vivo MRI of HI-injured mouse brains detected a shift of the tDKI peak to longer diffusion times, suggesting swelling of the cellular processes. Furthermore, we observed a faster decrease of the tDKI tail, reflecting increased transmembrane permeability associated with up-regulated water exchange or necrosis. Such information, unavailable from a single diffusion time, can predict salvageable tissues. Preliminary applications of tDKI in patients with ischemic stroke suggested increased transmembrane permeability in stroke regions, illustrating tDKI's potential for detecting pathological changes in the clinics.

21-Gene Recurrence Score and Survival Outcomes in the Phase III Multicenter TAILORx Clinical Trial.

Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population. We evaluated the association of RS with BCSS and OS plus recurrence-free interval (RFI) and invasive disease-free survival (DFS) using multivariable Cox proportional hazards regression analysis, adjusting for clinicopathologic measures, in 8,916 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer. Likelihood ratio (LR) test was used to assess the relative amount of prognostic information provided by RS to BCSS, OS, RFI, and DFS, comparatively. Event rates for BCSS, OS, RFI, and DFS were 1.7%, 5.2%, 5.6%, and 12.6%, respectively, by up to 11.6 years of follow-up. Compared with low-range RS (0-10), patients with midrange (11-25) and high-range (26-100) RS had inferior BCSS (adjusted hazard ratio [aHR], 5.12 [95% CI, 2.09-16.92] and 8.03 [95% CI, 2.91-28.47], respectively) and RFI (aHR, 1.68 [95% CI, 1.23-2.36] and 3.05 [95% CI, 2.02-4.67], respectively), independent of clinicopathologic factors. High-range score was associated with an increased risk of DFS (aHR, 1.56 [95% CI, 1.20-2.04]) but not significantly associated with OS (aHR, 1.44 [95% CI, 0.95-2.18]). Midrange score was associated with neither DFS (aHR, 1.15 [95% CI, 0.96-1.38]) nor OS (HR 1.14 [95% CI, 0.87-1.52]). LR-χ2 values were 83.0 and 65.1 for RFI and BCSS, respectively, and 17.5 and 33.6 for OS and DFS, respectively (P<.0001). RS is an independent measure for BCSS and recurrence prognoses relative to OS in early-stage breast cancer. It carries more prognostic information for breast cancer-specific outcomes.

Strain imaging as a prognostic indicator for complications in COVID-19 patients.

The goal of this study was to determine the potential for right ventricular (RV) and left ventricular (LV) strain to predict cardiopulmonary complications of COVID-19. We identified 276 patients with COVID-19 who underwent transthoracic echocardiography within 30 days of COVID-19 diagnosis at our institution. Patients were excluded if they had a history of any primary outcomes before COVID-19 diagnosis or insufficient imaging. LV global longitudinal strain (GLS) and RV GLS were obtained using 2-dimensional speckle-tracking echocardiography. Primary outcomes were death, pulmonary embolism, congestive heart failure (CHF), cardiomyopathy, pulmonary fibrosis, pulmonary hypertension, acute respiratory distress syndrome (ARDS), and myocardial infarction (MI) occurring after COVID-19 diagnosis. In the final analysis of 163 patients, mean RV GLS and LV GLS were reduced, and 43.6% developed at least one primary outcome. There were significant differences in LV GLS distribution in terms of CHF, cardiomyopathy, and MI in bivariate analysis. However, LV GLS was not significantly associated with CHF after adjusting for LV ejection fraction and RV fractional area change, nor with MI after adjusting for troponin T. RV GLS was significantly associated with ARDS after adjusting for other variables. In the risk stratification of patients with COVID-19, strain imaging can provide incremental prognostic information, as worsened RV GLS is associated with the development of ARDS.

Imaging and Metabolic Diagnostic Methods in the Stage Assessment of Rectal Cancer

Rectal cancer (RC) is a prevalent malignancy with significant morbidity and mortality rates. The accurate staging of RC is crucial for optimal treatment planning and patient outcomes. This review aims to summarize the current literature on imaging and metabolic diagnostic methods used in the stage assessment of RC. Various imaging modalities play a pivotal role in the initial evaluation and staging of RC. These include magnetic resonance imaging (MRI), computed tomography (CT), and endorectal ultrasound (ERUS). MRI has emerged as the gold standard for local staging due to its superior soft tissue resolution and ability to assess tumor invasion depth, lymph node involvement, and the presence of extramural vascular invasion. CT imaging provides valuable information about distant metastases and helps determine the feasibility of surgical resection. ERUS aids in assessing tumor depth, perirectal lymph nodes, and sphincter involvement. Understanding the strengths and limitations of each diagnostic modality is essential for accurate staging and treatment decisions in RC. Furthermore, the integration of multiple imaging and metabolic methods, such as PET/CT or PET/MRI, can enhance diagnostic accuracy and provide valuable prognostic information. Thus, a literature review was conducted to investigate and assess the effectiveness and accuracy of diagnostic methods, both imaging and metabolic, in the stage assessment of RC.

Evaluating surgeon communication of pancreatic cancer prognosis using the VitalTalk ADAPT framework.

Few data exist to guide optimal communication practices for surgical oncologists. VitalTalk, an evidence-based communication skills training model for clinicians, offers the five-step ADAPT tool for discussing prognosis. This study aimed to characterize surgeon communication of pancreatic cancer prognosis using VitalTalk's ADAPT framework. Contemporaneous audio recordings from 12 initial surgeon-patient encounters for borderline resectable pancreatic cancer were transcribed. Directed qualitative content analysis based on ADAPT (Ask, Discover, Anticipate, Provide, and Track) was used to deductively code transcripts. All encounters contained at least one ADAPT step while only one (8%) incorporated four or five steps. Surgeons provided prognostic information (Provide) in all but one encounter (92%); most was qualitative and clustered into themes: serious illness, surgical candidacy, prognostic ambiguity, and cancer recurrence. Surgeons elicited understanding (Ask), requested information preferences (Discover), anticipated ambivalence (Anticipate), and responded to emotion (Track) in a minority of encounters (25%-42%); of 15 patient emotional cues, six were not addressed by surgeons. During an initial encounter for pancreatic cancer, surgeons focus heavily on providing information but omit critical prognostic communication steps. Future studies are needed to investigate if surgeon training in palliative care-based communicationis feasible and impacts patient-perceived quality of communication.

Rapid and sensitive detection of heart-type fatty acid binding protein using aggregation-induced emission nanoparticles on digital microfluidics workstation

Early and rapid diagnostic of acute myocardial infarction (AMI) during its developing stage is crucial due to its high fatality rate. Heart-type fatty acid binding protein (h-FABP) is an ideal biomarker for the quantitative diagnosis of AMI, surpassing traditional markers such as myoglobin, creatine phosphokinase-MB, and troponin in terms of sensitivity, specificity, and prognostic value. To obtain diagnostic and prognostic information, a precise and fully quantitative measurement of h-FABP is essential, typically achieved through an immunosorbent assay like the enzyme-linked immunosorbent assay. Nevertheless, this method has several limitations, including extended detection time, complex assay procedures, the necessity for skilled technicians, and challenges in implementing automated detection. This research introduces a novel biosensor, utilizing aggregation-induced emission nanoparticles (AIENPs) and integrated with a digital microfluidic (DMF) workstation, designed for the sensitive, rapid, and automated detection of h-FABP in low-volume serum samples. AIENPs and magnetic beads in nanoscale were served as the capture particles and the fluorescent probe, which were linked covalently to anti-h-FABP antibodies respectively. The approach was based on a sandwich immunoassay and performed on a fully automated DMF workstation with assay time by 15 min. We demonstrated the determination of h-FABP in serum samples with detection limit of 0.14 ng/mL using this biosensor under optimal condition. Furthermore, excellent correlations (R2 = 0.9536, n = 50) were obtained between utilizing this biosensor and commercialized ELISA kits in clinical serum detecting. These results demonstrate that our flexible and reliable biosensor is suitable for direct integration into clinical diagnostics, and it is expected to be promising diagnostic tool for early detection and screening tests as well as prognosis evaluation for AMI patients.

Prognostic Value of Integrated Assessment of Cardiac Magnetic Resonance-Derived Global Coronary Flow Reserve and Cardiopulmonary Exercise Testing-Derived Peak Oxygen Consumption in Patients With Acute Myocardial Infarction.

Background: This study investigated the prognostic value of cardiovascular magnetic resonance (CMR)-derived global coronary flow reserve (G-CFR) in addition to cardiopulmonary exercise testing (CPET) variables in patients with acute myocardial infarction (AMI). Methods and Results: We investigated 127 patients with AMI who underwent primary or urgent percutaneous coronary intervention (PCI) and post-intervention CMR and CPET. The incidence of major cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent non-fatal myocardial infarction, re-hospitalization due to congestive heart failure, and stroke, was evaluated (median follow-up, 2.8 years). Patients with MACCE (n=14) had lower ejection fraction (EF) (50 [43-59] vs. 58 [51-63]%; P=0.014), lower G-CFR (1.74 [1.19-2.20] vs. 2.40 [1.61-3.66]; P=0.008), and lower peak oxygen consumption (V̇O2) (15.16±2.64 vs. 17.19±3.70 mL/kg/min; P=0.049) than patients without MACCE. G-CFR<2.33 and peak V̇O2 <15.65 mL/kg/min (cut-off values derived from receiver operating characteristic curve analyses) were significantly associated with the incidence of MACCE (log-rank test, P=0.01). The combination of low G-CFR and low peak V̇O2 improved risk discrimination for MACCE when added to the reference clinical model including age, male sex, post-PCI peak creatine kinase, EF, and left anterior descending artery culprit lesion. Conclusions: G-CFR and peak V̇O2 showed incremental prognostic information compared with the reference model using historically important clinical risk factors, indicating that this approach may help identify high-risk patients who suffer subsequent adverse events.

Left atrial and ventricular longitudinal strain by cardiac magnetic resonance feature tracking improves prognostic stratification of patients with ST-segment elevation myocardial infarction.

We aimed to investigate the predictive value of left atrium (LA) and left ventricle (LV) longitudinal strain derived by CMR-FT early after ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Patients with STEMI who received pPCI and completed CMR within the following week were enrolled. LA and LV longitudinal strain parameters were derived from cine CMR by FT; conventional CMR indexes were also performed. The primary endpoint was the occurrence of major cardiovascular adverse events (MACE), defined as a composite of death, reinfarction, and congestive heart failure (HF). 276 participants (median age, 57 years, IQR, 48-66 years; 85% men) were included in this study. CMR was usually completed on the 5 (IQR,4-7) days after pPCI. During a median follow-up of 16 months, MACE occurred in 35 (12.7%) participants. Multivariable Cox regression analysis showed that LA conduit strain (HR 0.91, 95%CI: 0.84, 0.98, p = 0.013) and LV global longitudinal strain (HR 1.17, 95%CI: 1.03, 1.34, p = 0.016) remained independently associated with MACE. Participants with impaired LA conduit strain (≤ 12.8%) and LV global longitudinal strain (> -13.1%) had a higher risk of MACE than those with preserved. Longitudinal strain of LA and LV could provide independent prognostic information in STEMI patients, and comprehensive assessment of Left atrial and ventricular longitudinal strain significantly improved the prognosis.

Left atrial and ventricular longitudinal strain by cardiac magnetic resonance feature tracking improves prognostic stratification of patients with ST-segment elevation myocardial infarction.

We aimed to investigate the predictive value of left atrium (LA) and left ventricle (LV) longitudinal strain derived by CMR-FT early after ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Patients with STEMI who received pPCI and completed CMR within the following week were enrolled. LA and LV longitudinal strain parameters were derived from cine CMR by FT; conventional CMR indexes were also performed. The primary endpoint was the occurrence of major cardiovascular adverse events (MACE), defined as a composite of death, reinfarction, and congestive heart failure (HF). 276 participants (median age, 57 years, IQR, 48-66 years; 85% men) were included in this study. CMR was usually completed on the 5 (IQR,4-7) days after pPCI. During a median follow-up of 16 months, MACE occurred in 35 (12.7%) participants. Multivariable Cox regression analysis showed that LA conduit strain (HR 0.91, 95%CI: 0.84, 0.98, p = 0.013) and LV global longitudinal strain (HR 1.17, 95%CI: 1.03, 1.34, p = 0.016) remained independently associated with MACE. Participants with impaired LA conduit strain (≤ 12.8%) and LV global longitudinal strain (> -13.1%) had a higher risk of MACE than those with preserved. Longitudinal strain of LA and LV could provide independent prognostic information in STEMI patients, and comprehensive assessment of Left atrial and ventricular longitudinal strain significantly improved the prognosis.

Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure

Background &amp; Rationale: Around 750.000 patients/year will be cured from hepatitis C-virus (HCV)-infection until 2030. Those with compensated advanced chronic liver disease (cACLD) remain at risk for hepatic decompensation and de-novo hepatocellular carcinoma (HCC). Algorithms have been developed to stratify risk early after cure, however, data on long-term outcome and the prognostic utility of these risk stratification algorithms at later timepoints are lacking. Main Results: We retrospectively analysed a cohort of 2335 cACLD-patients (LSM≥10kPa) who achieved HCV-cure by interferon-free therapies from 15 European centres (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes). During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate [IR]: 0.74%/year, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de-novo HCC (IR: 1.60%/year, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time. Baveno VII criteria to exclude (FU-LSM &lt;12kPa &amp; FU-PLT &gt;150 G/L) or rule-in (FU-LSM ≥25kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the grey-zone (i.e., patients meeting none of the above criteria). Published HCC risk stratification algorithms identified high- and low-incidence groups, however, the size of the latter group varied substantially (9.9%-69.1%). A granular ‘HCC-SVR’ model was developed to inform on an individual patient’s HCC-risk after HCV-cure. Conclusion: In patients with cACLD, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long-term (&gt;3 y). One-time post-treatment risk stratification based on non-invasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

Immunohistochemical analysis of tumor budding in stage II colon cancer: exploring zero budding as a prognostic marker.

Tumor budding, a biomarker traditionally evaluated using hematoxylin and eosin (H&E) staining, has gained recognition as a prognostic biomarker for stage II colon cancer. Nevertheless, while H&E staining offers valuable insights, its limitations prompt the utilization of pan-cytokeratin immunohistochemistry (IHC). Consequently, this study seeks to evaluate the prognostic significance of tumor budding using IHC in a contemporary cohort of stage II colon cancer patients, aiming to deepen our understanding of this critical facet in cancer prognosis. We conducted a retrospective, population-based cohort study including 493 patients with stage II colon cancer and evaluated tumor budding using IHC, following the H&E-based guidelines proposed by the International Tumor Budding Consensus Conference Group. Correlation between H&E-based and IHC-based tumor budding was assessed using a four-tiered scoring system that included a zero budding (Bd0) category. Survival analyses explored the prognostic significance of tumor budding assessed by IHC and H&E. As expected, IHC-based tumor budding evaluation yielded significantly higher bud counts compared to H&E (p < 0.01). Interestingly, 21 patients were identified with no tumor budding using IHC. This was associated with significantly improved recurrence-free survival (HR = 5.19, p = 0.02) and overall survival (HR = 4.47, p = 0.04) in a multivariate analysis when compared to tumors with budding. The Bd0 category demonstrated a 100% predictive value for the absence of recurrence. In conclusion, IHC-based tumor budding evaluation in stage II colon cancer provides additional prognostic information. The absence of tumor budding is associated with a favorable prognosis and may serve as a potential marker for identifying patients with no risk of recurrence.

Enhancing Immunotherapy Response Prediction in Metastatic Lung Adenocarcinoma: Leveraging Shallow and Deep Learning with CT-Based Radiomics across Single and Multiple Tumor Sites.

This study aimed to evaluate the potential of pre-treatment CT-based radiomics features (RFs) derived from single and multiple tumor sites, and state-of-the-art machine-learning survival algorithms, in predicting progression-free survival (PFS) for patients with metastatic lung adenocarcinoma (MLUAD) receiving first-line treatment including immune checkpoint inhibitors (CPIs). To do so, all adults with newly diagnosed MLUAD, pre-treatment contrast-enhanced CT scan, and performance status ≤ 2 who were treated at our cancer center with first-line CPI between November 2016 and November 2022 were included. RFs were extracted from all measurable lesions with a volume ≥ 1 cm3 on the CT scan. To capture intra- and inter-tumor heterogeneity, RFs from the largest tumor of each patient, as well as lowest, highest, and average RF values over all lesions per patient were collected. Intra-patient inter-tumor heterogeneity metrics were calculated to measure the similarity between each patient lesions. After filtering predictors with univariable Cox p < 0.100 and analyzing their correlations, five survival machine-learning algorithms (stepwise Cox regression [SCR], LASSO Cox regression, random survival forests, gradient boosted machine [GBM], and deep learning [Deepsurv]) were trained in 100-times repeated 5-fold cross-validation (rCV) to predict PFS on three inputs: (i) clinicopathological variables, (ii) all radiomics-based and clinicopathological (full input), and (iii) uncorrelated radiomics-based and clinicopathological variables (uncorrelated input). The Models' performances were evaluated using the concordance index (c-index). Overall, 140 patients were included (median age: 62.5 years, 36.4% women). In rCV, the highest c-index was reached with Deepsurv (c-index = 0.631, 95%CI = 0.625-0.647), followed by GBM (c-index = 0.603, 95%CI = 0.557-0.646), significantly outperforming standard SCR whatever its input (c-index range: 0.560-0.570, all p < 0.0001). Thus, single- and multi-site pre-treatment radiomics data provide valuable prognostic information for predicting PFS in MLUAD patients undergoing first-line CPI treatment when analyzed with advanced machine-learning survival algorithms.

Optimizing the use of Ki-67 proliferative index as a prognostic biomarker in meningiomas using digital analysis.

Ki-67 immunohistochemistry is widely used as a prognostic marker in meningiomas, but visual estimations tend to be imprecise. Whether the average Ki-67 over an entire slide, a particular block, or areas of high staining (hotspots) is prognostic for recurrence-free survival (RFS) and overall survival (OS) is unknown. This study aimed to generate evidence-based recommendations for the optimal use of Ki-67 immunohistochemistry in the workup of meningiomas. All tissue blocks from a retrospective cohort of 221 patients with primary meningioma (141 WHO grade 1, 64 WHO grade 2, 16 WHO grade 3) were immunostained for Ki-67 and scanned using automated digital analysis software. QuPath was used to quantify the average Ki-67 proliferation index per slide as well as the Ki-67 hotspot in a 2.2-mm2 area within each slide. The best block was defined subjectively by a neuropathologist as the most representative tissue block from each case. The pathology report Ki-67 was determined by visual estimation. Age, sex, WHO grade, extent of resection, tumor location, and quantitative Ki-67 labeling were tested to determine risk factors for RFS and OS. Multivariable analyses demonstrated that WHO grade 2 (HR 2.42, p = 0.018), subtotal resection (HR 8.16, p < 0.0001), near-total resection (HR 2.24, p = 0.041), QuPath Ki-67 averaged across all blocks (HR per % increase = 1.72, p = 0.030), and pathology report Ki-67 (HR per % increase = 1.05, p = 0.0026) were associated with shorter RFS. The average Ki-67 in the best block, maximum across all slides, and maximum hotspot in the best block were not associated with RFS. Only male sex was independently associated with shorter OS (HR 8.52, p = 0.0003). The pathology report Ki-67 was, on average, 6.5 times higher than the QuPath average. These data on Ki-67 in meningiomas indicate the following: 1) visual estimation substantially overestimates Ki-67, 2) digital quantification of average Ki-67 across all tissue blocks provides more prognostic information than small hotspot regions or an entire single block, and 3) Ki-67 is not informative for OS. The results suggest that best practices for incorporating Ki-67 into meningioma prognostication include digital quantification of average Ki-67 over multiple blocks.

Method of Diagnosing Sarcopenia in Morbidly Obese Patients

Introduction. Sarcopenia refers to a clinical syndrome characterized by progressive skeletal muscle disease, loss of muscle mass and strength resulting in impaired physical performance. The prevalence of sarcopenia in the population ranges from 5% to 13% in people aged 43.0 ± 11.1 years and reaches 50% in those over 70. Various methods have been used to diagnose sarcopenia, which, however, have their limitations. Currently, CT scanning is considered the most accurate method for the detection of sarcopenia. Therefore, the development of new methods for early diagnosis of sarcopenia appears relevant. Aim. To investigate different methods of diagnosing sarcopenia in morbidly obese patients. Materials and methods. The study presents an analysis of various methods for diagnostics of sarcopenia in morbidly obese patients, including a patented method based on the research conducted in the BSMU Clinic (Utility Patent No. 2815157 dated 11.03.2024). Results and discussion. Doctors used the suggested method of diagnosis, defined the value of sarcopenia index equal or less than 15, and diagnosed sarcopenia. Conclusion. The prevalence and severity of sarcopenia vary depending on the classification criteria and thresholds used. Since a unified diagnostic method is yet to be developed, it is necessary to continue research into this issue, and introduce sarcopenia detection, prevention, and correction techniques into widespread clinical practice. Indices of sarcopenia and obesity, obtained during an additional preoperative study, provide significant prognostic information superior to body mass index, thereby enabling the direction and scope of surgical interventions to be determined and survival outcomes to be improved.

Method of Diagnosing Sarcopenia in Morbidly Obese Patients

Introduction. Sarcopenia refers to a clinical syndrome characterized by progressive skeletal muscle disease, loss of muscle mass and strength resulting in impaired physical performance. The prevalence of sarcopenia in the population ranges from 5% to 13% in people aged 43.0 ± 11.1 years and reaches 50% in those over 70. Various methods have been used to diagnose sarcopenia, which, however, have their limitations. Currently, CT scanning is considered the most accurate method for the detection of sarcopenia. Therefore, the development of new methods for early diagnosis of sarcopenia appears relevant. Aim. To investigate different methods of diagnosing sarcopenia in morbidly obese patients. Materials and methods. The study presents an analysis of various methods for diagnostics of sarcopenia in morbidly obese patients, including a patented method based on the research conducted in the BSMU Clinic (Utility Patent No. 2815157 dated 11.03.2024). Results and discussion. Doctors used the suggested method of diagnosis, defined the value of sarcopenia index equal or less than 15, and diagnosed sarcopenia. Conclusion. The prevalence and severity of sarcopenia vary depending on the classification criteria and thresholds used. Since a unified diagnostic method is yet to be developed, it is necessary to continue research into this issue, and introduce sarcopenia detection, prevention, and correction techniques into widespread clinical practice. Indices of sarcopenia and obesity, obtained during an additional preoperative study, provide significant prognostic information superior to body mass index, thereby enabling the direction and scope of surgical interventions to be determined and survival outcomes to be improved.

The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors.

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59-3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01-1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56-0.75) and 0.60 (0.51-0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68-0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74-0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69-0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Is the burden of metastatic lymph node stations a prognostic factor in patients with resected lung cancer?

ObjectivesThe burden of metastatic lymph node (LN) stations might reflect a distinct N subcategory with a more aggressive biology and behaviour than the traditional N classification.MethodsBetween 2008 and 2018, we analyzed 1236 patients with pN1/2 lung cancer. Survival was analyzed based on LN station metastasis, determining the optimal threshold for the number of metastatic LN stations that provided additional prognostic information. N prognostic subgrouping was performed using thresholds for the number of metastatic LN stations with the maximum chi-square log-rank value, and validated at each pT-stage.ResultsSurvival showed stepwise statistical deterioration with an increase in the number of metastatic LN stations., Threshold values for the number of metastatic LN stations were determined and N prognostic subgroupswas created as sN-alpha; one LN station metastases (n = 632), sN-beta; two-three LN stations metastases (n = 505), and sN-gamma; ≥4 LN stations metastasis (n = 99). The 5-year survival rate was 57.7% for sN-alpha, 39.2% for sN-beta, and 12.7% for sN-gamma (chi-square log rank = 97.906, p < 0.001). A clear tendency of survival deterioration was observed from sN-alpha to sN-gamma in the same pT stage, except for pT4 stage. Multivariate analysis showed that age (p < 0.001), sex (p = 0.002), tumour histology (p < 0.001), IASLC-proposed N subclassification (p < 0.001), and sN prognostic subgroups (p < 0.001) were independent risk factors for survival.ConclusionThe burden of metastatic LN stations is an independent prognostic factor for survival in patients with lung cancer. It could provide additional prognostic information to the N classification.

Early ctDNA kinetics as a dynamic biomarker of cancer treatment response.

Circulating tumor DNA assays are promising tools for the prediction of cancer treatment response. Here, we build a framework for the design of ctDNA biomarkers of therapy response that incorporate variations in ctDNA dynamics driven by specific treatment mechanisms. We develop mathematical models of ctDNA kinetics driven by tumor response to several therapy classes, and utilize them to simulate randomized virtual patient cohorts to test candidate biomarkers. Using this approach, we propose specific biomarkers, based on ctDNA longitudinal features, for targeted therapy, chemotherapy and radiation therapy. We evaluate and demonstrate the efficacy of these biomarkers in predicting treatment response within a randomized virtual patient cohort dataset. These biomarkers are based on novel proposals for ctDNA sampling protocols, consisting of frequent sampling within a compact time window surrounding therapy initiation - which we hypothesize to hold valuable prognostic information on longer-term treatment response. This study highlights a need for tailoring ctDNA sampling protocols and interpretation methodology to specific biological mechanisms of therapy response, and it provides a novel modeling and simulation framework for doing so. In addition, it highlights the potential of ctDNA assays for making early, rapid predictions of treatment response within the first days or weeks of treatment, and generates hypotheses for further clinical testing.

Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy)indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Coronary Artery Disease Is A Stronger Predictor of All-Cause Mortality Than Left Ventricular Ejection Fraction Among Patients With Newly Diagnosed Heart Failure: Insights From the WDHR.

In patients with newly diagnosed heart failure (HF) and left ventricular ejection fraction (LVEF) <50%, little is known whether LVEF per se or presence of coronary artery disease (CAD) provides independent prognostic information on all-cause mortality. Using the WDHR (Western Denmark Heart Registry), we identified 3620 patients with newly diagnosed HF and LVEF 10% to 49% referred for first-time coronary angiography as part of general workup of HF. Patients were stratified by LVEF (10%-35% versus 36%-49%) and presence of CAD. We estimated 10-year all-cause mortality risk and calculated hazard ratios adjusted for relevant comorbidities and risk factors (aHRs). CAD was present in 1592 (44%) patients. Lower LVEF was associated with a relative 15% increased 10-year mortality: 37% for LVEF 36% to 49% versus 42% for LVEF 10% to 35% (aHR, 1.15 [95% CI, 0.99-1.34]). This result did not change when stratified into those with CAD (52% versus 56%; aHR, 1.11 [95% CI, 0.91-1.35]) and those without CAD (27% versus 33%; aHR, 1.24 [95% CI, 0.97-1.57]). In comparison, presence and extent of CAD were associated with a relative 43% increased 10-year mortality (CAD versus no CAD, 55.0% versus 31.5%; aHR, 1.43 [95% CI, 1.25-1.64]). Compared with a matched general population, excess mortality risk was higher for patients with HF and CAD (54.7% versus 26.3%; aHR, 2.10 [95% CI, 1.85-2.39]) versus those with HF and no CAD (31.4% versus 17.2%; aHR, 1.76 [95% CI, 1.52-2.02]). Among newly diagnosed patients with HF and LVEF <50%, presence and extent of CAD are associated with substantial higher all-cause mortality risk than lower LVEF.