MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

BACKGROUND: Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma. PROCEDURE: Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961. Comparisons of clinical and biologic features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free (EFS) and overall (OS) survival compared using log-rank tests and modeled using Cox models. RESULTS: Thirty of 343 patients (8.7%) had MIBG nonavid disease. Patients with nonavid tumors were less likely to have adrenal primary tumors (34.5 vs. 57.2%; P = 0.019), bone metastases (36.7 vs. 61.7%; P = 0.008), or positive urine catecholamines (66.7 vs. 91.0%; P < 0.001) compared with patients with MIBG avid tumors. Nonavid tumors were more likely to be MYCN amplified (53.8 vs. 32.6%; P = 0.030) and had lower norepinephrine transporter expression. Patients with MIBG nonavid disease had a 5-year EFS of 50.0% compared with 38.7% for patients with MIBG avid disease (P = 0.028). On multivariate testing in high-risk patients, MIBG avidity was the sole adverse prognostic factor for EFS identified (hazard ratio 1.77; 95% confidence interval 1.04-2.99; P = 0.034). CONCLUSIONS: Patients with MIBG nonavid neuroblastoma have lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN-amplified tumors, these patients have superior outcomes compared with patients with MIBG avid disease.

Post-Capillary Pulmonary Hypertension: Clinical Review.

Pulmonary hypertension (PH) caused by left heart disease, also known as post-capillary PH, is the most common etiology of PH. Left heart disease due to systolic dysfunction or heart failure with preserved ejection fraction, valvular heart disease, and left atrial myopathy due to atrial fibrillation are causes of post-capillary PH. Elevated left-sided filling pressures cause pulmonary venous congestion due to backward transmission of pressures and post-capillary PH. In advanced left-sided heart disease or valvular heart disease, chronic uncontrolled venous congestion may lead to remodeling of the pulmonary arterial system, causing combined pre-capillary and post-capillary PH. The hemodynamic definition of post-capillary PH includes a mean pulmonary arterial pressure > 20 mmHg, pulmonary vascular resistance < 3 Wood units, and pulmonary capillary wedge pressure > 15 mmHg. Echocardiography is important in the identification and management of the underlying cause of post-capillary PH. Management of post-capillary PH is focused on the treatment of the underlying condition. Strategies are geared towards pharmacotherapy and guideline-directed medical therapy for heart failure, surgical or percutaneous management of valvular disorders, and control of modifiable risk factors and comorbid conditions. Referral to centers with advanced heart and pulmonary teams has shown to improve morbidity and mortality. There is emerging interest in the use of targeted agents classically used in pulmonary arterial hypertension, but current data remain limited and conflicting. This review aims to serve as a comprehensive summary of postcapillary PH and its etiologies, pathophysiology, diagnosis, and management, particularly as it pertains to advanced heart failure.

Volume Doubling Time of Pulmonary Carcinoid Tumors Measured by Computed Tomography.

INTRODUCTION: Pulmonary carcinoid tumor (PCT) is a rare neuroendocrine lung neoplasm comprising approximately 2% of lung cancer diagnoses. It is classified as either localized low-grade (typical) or intermediate-grade (atypical) subtypes. PCT is known clinically to be a slow-growing cancer, however few studies have established its true growth rate when followed over time by computed tomography (CT). Therefore, we sought to determine the volume doubling time for PCTs as visualized on CT imaging. MATERIALS AND METHODS: We conducted a retrospective analysis of all PCTs treated at our institution between 2006 and 2020. Nodule dimensions were measured using a Picture Archiving and Communication System or retrieved from radiology reports. Volume doubling time was calculated using the Schwartz formula for PCTs followed by successive CT scans during radiographic surveillance. Consistent with Fleischner Society guidelines, tumors were considered to have demonstrated definitive growth by CT only when the interval change in tumor diameter was greater than or equal to 2 mm. RESULTS: The median volume doubling time of 13 typical PCTs was 977 days, or 2.7 years. Five atypical PCTs were followed longitudinally, with a median doubling time of 327 days, or 0.9 years. CONCLUSIONS: Typical pulmonary carcinoid features a remarkably slow growth rate as compared to more common lung cancers. Our analysis of atypical pulmonary carcinoid included too few cases to offer definitive conclusions. It is conceivable that clinicians following current nodule surveillance guidelines may mistake incidentally detected typical carcinoids for benign non-growing lesions when followed for less than 2 years in low-risk patients.

Differences in Genomic Profiles and Outcomes Between Thoracic and Adrenal Neuroblastoma.

BACKGROUND: Neuroblastoma is a biologically and clinically heterogeneous disease. Based on recent studies demonstrating an association between the primary tumor site, prognosis, and commonly measured tumor biological features, we hypothesized that neuroblastomas arising in different sites would show distinct genomic features reflective of the developmental biology of the sympathicoadrenal nervous system. METHODS: We first compared genomic and epigenomic data of primary diagnostic neuroblastomas originating in the adrenal gland (n = 646) compared to thoracic sympathetic ganglia (n = 118). We also evaluated association of common germline variation with these primary sites in 1027 European-American neuroblastoma patients. RESULTS: We observed higher rates of MYCN amplification, chromosome 1q gain, and chromosome 11q deletion among adrenal tumors, which were highly predictive of functional RNA signatures. Surprisingly, thoracic neuroblastomas were more likely to harbor ALK driver mutations than adrenal cases among all cases (odds ratio = 1.89, 95% confidence interval = 1.04 to 3.43), and among cases without MYCN amplification (odds ratio = 2.86, 95% confidence interval = 1.48 to 5.49). Common germline single nucleotide polymorphisms (SNPs) in BARD1 (previously associated with high-risk neuroblastoma) were found to be strongly associated with predisposition for origin at adrenal, rather than thoracic, sites. CONCLUSIONS: Neuroblastomas arising in the adrenal gland are more likely to harbor structural DNA aberrations including MYCN amplification, whereas thoracic tumors show defects in mitotic checkpoints resulting in hyperdiploidy. Despite the general association of ALK mutations with high-risk disease, thoracic tumors are more likely to harbor gain-of-function ALK aberrations. Site of origin is likely reflective of stage of sympathetic nervous system development when malignant transformation occurs and is a surrogate for underlying tumor biology.