The Biological Behavior of High-Grade Glioma in H3K27M Mutant Circumscribed Midline Gliomas

Purpose Due to the prognosis of circumscribed middle gliomas（CMGs）with H3K27M mutation is still unclear. This study explored the prognostic stratification of （CMGs） with H3K27M mutation.Methods: One hundred and sixty middle gliomas（MGs）were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and P53, and Sanger sequencing performed for IDH and H3 genes. The clinicopathological characteristics were reviewed and survival analysis performed.Results: 1. H3K27M mutation was associated with a poor prognosis (p = 0.00017) for brainstem gliomas, but not for thalamic gliomas (p = 0.3). In the elder adults (≥40 years), there was no correlation between H3K27M mutation and the prognosis for MGs (p = 0.49).2. For H3K27M mutant MGs, there was no difference in prognosis between diffuse midline gliomas (DMGs) and CMGs (p = 0.211), also between the CNS WHO grades.3. The prognosis of H3K27M mutant CMGs of CNS WHO grade 1 was worse than that of H3K27M wild-type CMGs (p = 0.0024), even worse than of DMGs without H3K27M mutation of CNS WHO grade 2(p = 0.0066). There was no significant difference in prognosis from DMGs with histological grades CNS WHO grade 3 and 4 (p = 0.46).Conclusions: The weight value of H3K27M affecting prognosis is affected by location and age. CMGs with H3K27M mutation have biological behavior similar to high-grade gliomas. It is recommended that Treatment management was referenced to high-grade glioma for CMGs with H3K27 mutation.

Prognostic and Therapeutic Implications of Tumor Biology in Colorectal Liver Metastases

Prognostic models allow clinicians to predict survival outcomes, facilitate patient–physician discussions, and identify subgroups with potentially distinct prognoses. Although such prognostic stratification cannot directly predict treatment benefit, it can help to inform clinical decision making. This editorial will discuss potential avenues for these topics in the context of colorectal cancer liver metastases (CRLM)[...]

An Overview of Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors are a group of endocrine tumors that constitute 7% of all pancreatic neoplasms. They can be benign or malignant. Their presentation can vary from slow growing, non infiltrative, indolent masses to rapidly progressing, highly aggressive, metastasizing tumors. In the past, there was paucity of scientific data available about the diagnosis and treatment strategy of these neoplasms but in recent years, ongoing research has inferred much data regarding classification, prognostic stratification and therapy of pancreatic neuroendocrine tumors. In this chapter we will discuss epidemiology, clinical presentation and classification, diagnosis and management of these tumors. We will also deliberate about the latest developments in treatment of pancreatic neuroendocrine tumors with focus on recent studies done on this topic.

351 Prevalence and prognostic significance of RV uptake (biventricular uptake) at planar scintigraphy in patients with ATTR cardiac amyloidosis

Aims The validation of cardiac scintigraphy with bone tracers for nonbiopsy confirmation of transthyretin cardiac amyloidosis (ATTR-CA) has revolutionized the diagnosis of this condition. While most studies focused on left ventricle (LV) uptake, the significance of bone tracers uptake in the right ventricle (RV) leading to biventricular (BiV) uptake has not been investigated so far. BiV uptake at planar scintigraphy might reflect a more advanced ATTR-CA. To estimate the prevalence of BiV uptake and its potential prognostic role in ATTR-CA. Methods and results Multicentre, retrospective, observational study performed among four Italian referral centres for CA. Data of ATTR-CA patients who underwent bone tracers scintigraphy with acquisition of planar and SPECT imaging between November 2014 and June 2020 at participating centres were centrally revised. ATTR-CA was diagnosed according to the Gilmore’s algorithm. LV uptake was assessed by Perugini visual scale. RV uptake was defined as: 0 = absent, 1 ≤ bone uptake, 2 = equal to bone uptake, and 3 ≥ bone uptake. Images were independently assessed by six experienced operators, blinded to all patients’ data. Cardiological data included clinical examination, ECG, echocardiography and blood tests. The primary outcome was a composite of cardiac death and hospitalization for heart failure. Of the 124 patients with ATTR-CA included in this analysis, 93 (75%) had BiV uptake at planar scintigraphy and all had RV free wall uptake confirmed at SPECT imaging. The prevalence of planar BiV uptake increased along with the LV Perugini grade: 14% in Perugini grade 1, 70% in Perugini grade 2, and 92% in Perugini grade 3. Compared to those with planar LV uptake, patients with planar BiV uptake were older (81 vs. 77 years, P = 0.006), more frequently in NYHA ≥3 (32% vs. 10%, P = 0.018), had increased NT-proBNP values (4293 vs. 2492 pg/ml, P = 0.046), LV wall thickness (18 vs. 17 mm, P = 0.007). They had higher rates of LV ejection fraction <50% (42% vs. 10%, P = 0.001) and lower TAPSE (16 vs. 20 mm, P = 0.048). At 18 months, patients with BiV uptake experienced the primary endpoint more frequently than those with LV uptake (P = 0.021, Figure), with the highest risk observed in patients with grade 2–3 RV uptake (P = 0.010). The LV Perugini grade did not affect prognosis (P = 0.20). At multivariate analysis, NYHA ≥3, eGFR <60 ml/min and BiV uptake had independent prognostic value (HR 8.0, P = 0.007; HR 2.1, P = 0.025; HR 1.7, P = 0.007; respectively). Conclusions The presence of BiV uptake at planar scintigraphy identified ATTR-CA patients at worse cardiovascular outcome, potentially serving as novel marker for prognostic stratification in this population.

Prognostic stratification for patients with neuroendocrine tumours receiving 177Lu-Dotatate

177Lu-Dotatate is increasingly used in patients with advanced neuroendocrine tumour (NET). However, few prognostic markers are available to stratify progression-free survival (PFS) of patients received 177Lu-Dotatate. Clinicopathological data, including baseline circulating biomarkers of patients with advanced NET received 177Lu-Dotatate that were routinely collected were retrospectively analysed. Continuous variables were normalized by dividing them by their upper normal limits. The whole dataset was randomly divided into a training set and a validation set. Univariate and multivariate logistic regression analysis were used to identify independent markers and develop a scoring model to predict treatment failure at 1-year. In total, 195 patients were included. Elevated baseline chromogranin A (CgA), normal creatinine and previous chemotherapy were three risk factors independently associated with 1-year treatment failure. By combining these risk factors, a scoring model was developed which could accurately predict 1-year treatment failure both in the training set (area under curve, AUC, 0.813; 95% confidence interval, 95%CI, 0.731-0.895; P<0.001) and the validation set (ACU, 0.816; 95%CI, 0.644-0.968; P<0.001). After selecting a score of 29.7 as the cutoff value of the scoring model, patients could be stratified into two groups, low-risk and high-risk with significantly different 1-year treatment failure rate, PFS and overall survival (OS; P<0.001) both in training set and validation set. In conclusion, baseline CgA, creatinine level, and previous chemotherapy were independently associated with 1-year treatment failure of patients with advanced NET who received 177Lu-Dotatate and the scoring model and prognostic stratification based on these markers could accurately predict 1-year treatment failure, PFS and OS.