Development of a radiomics model to diagnose pheochromocytoma preoperatively: a multicenter study with prospective validation

Background Preoperative diagnosis of pheochromocytoma (PHEO) accurately impacts preoperative preparation and surgical outcome in PHEO patients. Highly reliable model to diagnose PHEO is lacking. We aimed to develop a magnetic resonance imaging (MRI)-based radiomic-clinical model to distinguish PHEO from adrenal lesions. Methods In total, 305 patients with 309 adrenal lesions were included and divided into different sets. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction, feature selection, and radiomics signature building. In addition, a nomogram incorporating the obtained radiomics signature and selected clinical predictors was developed by using multivariable logistic regression analysis. The performance of the radiomic-clinical model was assessed with respect to its discrimination, calibration, and clinical usefulness. Results Seven radiomics features were selected among the 1301 features obtained as they could differentiate PHEOs from other adrenal lesions in the training (area under the curve [AUC], 0.887), internal validation (AUC, 0.880), and external validation cohorts (AUC, 0.807). Predictors contained in the individualized prediction nomogram included the radiomics signature and symptom number (symptoms include headache, palpitation, and diaphoresis). The training set yielded an AUC of 0.893 for the nomogram, which was confirmed in the internal and external validation sets with AUCs of 0.906 and 0.844, respectively. Decision curve analyses indicated the nomogram was clinically useful. In addition, 25 patients with 25 lesions were recruited for prospective validation, which yielded an AUC of 0.917 for the nomogram. Conclusion We propose a radiomic-based nomogram incorporating clinically useful signatures as an easy-to-use, predictive and individualized tool for PHEO diagnosis.

Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients

Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004-2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Pathophysiology, Diagnosis, and Management of Coronary No-Reflow Phenomenon

Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but they have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon.

Universal Germline Panel Testing for Individuals with Pheochromocytoma and Paraganglioma Produces High Diagnostic Yield

Background Practice guidelines to identify individuals with hereditary pheochromocytomas and paragangliomas (PPGLs) advocate for sequential gene testing strategy guided by specific clinical features and predate the routine use of multigene panel testing (MGPT). Objective To describe results of MGPT for hereditary PPGL in a clinically and ancestrally diverse cohort. Setting Commercial laboratory based in the United States. Methods Clinical data and test results were retrospectively reviewed in 1727 individuals who had targeted MGPT due to suspicion of hereditary PPGL from August 2013 through December 2019. Results Overall, 27.5% of individuals had a pathogenic or likely pathogenic variant (PV), 9.0% had a variant of uncertain significance, and 63.1% had a negative result. Most PVs were identified in SDHB (40.4%), followed by SDHD (21.1%), SDHA (10.1%), VHL (7.8%), SDHC (6.7%), RET (3.7%), and MAX (3.6%). PVs in FH, MEN1, NF1, SDHAF2, and TMEM127 collectively accounted for 6.5% of PVs. Clinical predictors of a PV included extra-adrenal location, early age of onset, multiple tumors, and positive family history of PPGL. Individuals with extra-adrenal PGL and a positive family history were the most likely to have a PV (85.9%). Restricting genetic testing to SDHB/C/D misses a third (32.8%) of individuals with PVs. Conclusion Our data demonstrate a high diagnostic yield in individuals with and without established risk factors, a low inconclusive result rate, and a substantial contribution to diagnostic yield from rare genes. These findings support universal testing of all individuals with PPGL and the use of concurrent MGPT as the ideal platform.

Clinical Predictors of Survival for Patients with Atypical Teratoid/Rhabdoid Tumors

Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). Methods: Information was collected on patients with histologically-confirmed AT/RT using the NCDB (2004-2016). Kaplan-Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional-hazards (CPH) and logistic regression models. Results: Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7±2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS=5.91 months), 51 (27.7%) received surgery and chemotherapy (S+CT) (OS=11.2 months), and 9 (4.89%) received surgery and radiotherapy (S+RT) (OS=10.3 months). Forty-five (24.5%) received S+CT+RT combination therapy (OS=45.4 months), 13 (17.1%) received S+CT+BMT/SCT (bone marrow or stem cell transplant) (OS=55.5 months), and 16 (8.70%) received S+CT+RT+BMT/SCT (OS=68.4 months). Bivariate analysis of dichotomized age (HR=0.550, 95% CI[0.357, 0.847], p=0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S+CT+RT, S+CT+BMT/SCT, or S+CT+RT+BMT/SCT combination therapy predicted significantly (p<0.05) increased OS compared to surgery alone. Conclusion: AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low.

Clinical Determinants and Prognosis of Left Ventricular Reverse Remodelling in Non-Ischemic Dilated Cardiomyopathy

Aims: Non-ischaemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of coronary artery disease. Left ventricular reverse remodelling (LVRR) is the ability of a dilated ventricle to restore its normal size, shape and function. We sought to determine the frequency, clinical predictors and prognostic implications of LVRR, in a cohort of heart failure (HF) patients with NIDCM. Methods: We conducted a multicentre observational, retrospective cohort study of patients with NIDCM, with prospective serial echocardiography evaluations. LVRR was defined as an increase of ≥15% in left ventricular ejection fraction (LVEF) or as a LVEF increase ≥ 10% plus reduction of LV end-systolic diameter index ≥ 20%. We used multivariable logistic regression analyses to identify the baseline clinical predictors of LVRR and evaluate the prognostic impact of LVRR. Results: LVRR was achieved in 42.5% of 527 patients with NIDCM during the first year of follow-up (median LVEF 49%, median change +22%), Alcoholic aetiology, HF duration, baseline LVEF and the absence of LBBB (plus NT-proBNP levels when in the model), were the strongest predictors of LVRR. During a median follow-up of 47 months, 134 patients died (25.4%) and 7 patients (1.3%) received a heart transplant. Patients with LVRR presented better outcomes, regardless of other clinical conditions. Conclusions: In patients with NIDCM, LVRR was frequent and was associated with improved prognosis. Major clinical predictors of LVRR were alcoholic cardiomyopathy, absence of LBBB, shorter HF duration, and lower baseline LVEF and NT-proBNP levels. Our study advocates for clinical phenotyping of non-ischaemic dilated cardiomyopathy and intense gold-standard treatment optimization of patients according to current guidelines and recommendations in specialized HF units.

Demographic and Clinical Predictors of Engaging in Tobacco Cessation Counseling at a Comprehensive Cancer Center

PURPOSE: To address challenges promoting tobacco cessation in oncology settings, it is important to understand characteristics associated with patient engagement in tobacco cessation treatment. This analysis examined predictors of participating in at least one tobacco cessation counseling session among patients referred to a comprehensive cancer center's Tobacco Intervention and Psychosocial Support (TIPS) service. METHODS: Patients with cancer who reported current smoking or recently quitting and referred to TIPS between June 2017 and February 2020 were included in the analysis. Independent variables included sex, race and ethnicity, insurance type, cancer diagnosis (tobacco-related or not), age, nicotine dependence, and cigarettes smoked per day at baseline. The outcome variable was completion of at least one tobacco cessation counseling session among those assessed by the TIPS program. Unadjusted and adjusted analyses tested associations between the independent variables and tobacco cessation counseling engagement. RESULTS: Of 360 oncology patients referred to the TIPS program, 224 (62.2%) were assessed and 120 (33%) engaged in at least one counseling session. After controlling for sociodemographics and tobacco use, the results demonstrated that patients diagnosed with tobacco-related cancers were 45.3% less likely to engage in the tobacco cessation program compared with those with non–tobacco-related cancers ( P = .041). CONCLUSION: Patients diagnosed with tobacco-related cancers were less likely to engage in TIPS. Additional therapeutic resources may be needed to engage these patients to address potential explanatory factors, such as stigma, guilt, and fatalism. More research is needed to explore the impact of a tobacco-related cancer diagnosis on treatment engagement.