Diagnosis and treatment for pure aqueductal tumor

Pure aqueductal tumor (PAT) typically originates from pure aqueductal region and is extremely rare. It is radiographically similar to tectal glioma. We examined two patients with PATs who were diagnosed with pilocytic astrocytoma and rosette-forming glioneuronal tumor. Both cases showed a progressive clinical course. It is important to distinguish between PAT and tectal glioma by radiographic imaging because the treatment strategy is different. While observation is common for tectal gliomas, a biopsy is recommended at the same time of endoscopic third ventriculostomy for PAT with hydrocephalus. Low-grade PATs show an aggressive clinical course in some cases. Our two cases also showed aggressive course in spite of no genetic aggressive mutations. Sagittal view by constructive interference in steady state (CISS) imaging was helpful to make an accurate diagnosis of PAT. Close observation is needed if PAT is diagnosed as low-grade tumor.     

Stage-specific prognostic biomarkers in melanoma

The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.     

甲状腺乳头状癌突变等位基因肿瘤异质性的临床及其与预后相关性研究

目的探讨突变等位基因肿瘤异质性(MATH)在甲状腺乳头状癌（PTC）中的临床意义。 方法从癌症基因图谱公共数据集下载并预处理PTC肿瘤测序数据及临床资料数据，分析MATH与PTC临床病理特征的相关性，使用Kaplan-Meier法进行生存分析，验证MATH对PTC患者的预后价值。 结果PTC患者中MATH值为2.57~93.72，平均29.45±16.19；将≥29.45者纳入高MATH组，<29.45者纳入低MATH组。高MATH组与低MATH组的患者年龄、性别、临床分期、BRAF基因型差异无统计学意义（P>0.05）。MATH不是PTC患者总体生存期（OS）的显著预测因素（P=0.4595）；在BRAF突变型PTC患者中，高MATH者的OS低于低MATH者（P=0.0252），而在BRAF野生型PTC患者中，高MATH者的OS高于低MATH者（P=0.0495）。 结论MATH可在BRAF突变型和野生型亚组中可预测PTC患者的预后及指导临床治疗。     

Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations

Introduction: Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAF^V600 mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge.

Areas covered: Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/MEK inhibitor combinations.

Expert opinion: While other BRAF/MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive melanoma treated with encorafenib plus binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial. PFS also appears to be improved with encorafenib plus binimetinib. This improved efficacy may be related to the distinct pharmacokinetics of encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of pyrexia and photosensitivity. Encorafenib plus binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/MEK inhibitor combinations.     

Toxicité rénale des anticancéreux

The renal toxicity of anticancer drugs is a clinical challenge because of the intrinsic toxicity of some anticancer drugs and because the cancer itself. Indeed, cancer patients are exposed to all types of renal disorders (obstructive, functional, organic because of radiotherapy, paraneoplastic glomerulopathy, thrombotic microangiopathy…). The therapeutic index of anticancer drugs is often narrow and the doses used for optimal efficacy are high. Improving safety requires a better dose adjustment, which depends on the correct evaluation of the renal function. Prevention remains important as the mortality associated with acute renal failure is very high.     

Discrepancy in BRAF status among patients with metastatic malignant melanoma: A meta-analysis

The incidence of malignant melanoma is growing rapidly. Approximately half of the cases are BRAF mutated, making treatment with kinase inhibitors a (MEK and BRAF inhibitors) preferred choice in the advanced setting. The vast majority of these patients will benefit from the treatment. It is therefore of vital importance that the BRAF analysis is reliable and reflects the true nature of the tumour. Intraindividual tumour BRAF heterogeneity may exist, and changes of BRAF status over time might occur.We reviewed the literature by searching the PubMed database and 630 potentially relevant studies were identified. Thereafter, studies that investigated intralesional heterogeneity only, studies with ≤10 patients and studies that did not include adequate data to calculate discrepancy rates were excluded. Twenty-two studies met our inclusion criteria and were included in the meta-analysis.The pooled discrepancy rate between primary and metastatic lesions was 13.4% (95% confidence interval [CI]: 9.2–18.2%) while it was 7.3% (95% CI: 3.3–12.6) between two metastatic lesions. The number of patients whose tumoural BRAF status was changed from mutation to wild type and from wild type to mutation, respectively, was comparable.We conclude that a clinically meaningful discrepancy rate in BRAF status both between primary-metastatic and metastatic–metastatic melanoma lesions exists. Our results support the polyclonal model of melanomas in which subclones with different BRAF status co-exist in the same melanoma lesion. In addition, the results indicate a need for biopsy of a metastatic lesion for subsequent BRAF analysis when treatment with kinase inhibitors is considered.