Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).     

Significance of 18F-FDG PET/CT in Characterization of Equivocal Lesions in High-Risk Testicular Carcinoma in Restaging Setting

Objectives: The present study aims to evaluate the role of Positron emission tomography (PET) -computed tomography (CT) with 18F-fluorodeoxyglucose (18F-FDG) in the restaging of high-risk testicular cancer. Methods: Forty-five patients (mean age of 38.1±11.3 years and range 23-81 years) with testicular carcinoma, underwent 18F-FDG PET-CT during their clinical course were prospectively selected. PET positivity was defined as a site of abnormal 18F-FDG uptake in tissue histologically proven or clinically or radiographically suspected to represent tissue involvement. The sites of disease were characterized as either nodal or extranodal. All patients were followed-up for at least 12 months with a diagnostic and/or functional imaging modality. Results: Of the 45 patients 38 (84%) patient presented with seminoma and 7 (16%) were Non-seminomatous germ cell tumors. Analysis of secondary disease spectrum showed nodal involvement in 65%, osseous involvement in 23% and mixed visceral/soft tissue lesions in 12% of patients. Nineteen (42%) were negative for any metastatic disease. All negative patients remain disease free in the follow-up of one year. Out of the positive 26/45 patients, PET-CT showed progressive disease in 3/26, stable disease 1/26 and partial response in 2/26 and complete metabolic resolution in 20/26 patients. 18F-FDG PET-CT was able to characterize all patients leading to significant change of primary decision of wait and watch to go for treatment and vice versa. Conclusion: 18F-FDG PET-CT scan is potentially an excellent tool for characterization of equivocal lesions on CT scan in the restaging settings and follow up of high-risk testicular cancer patients.     

Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms. Using differential centrifugation, EVs were isolated from established sorafenib-resistant RCC cells (786-0 and ACHN), and EVs derived from sorafenib-resistant cells were uptaken by sensitive parental RCC cells and thus promoted drug resistance. Elevated exogenous miR-31-5p within EVs effectively downregulated MutL homolog 1 (MLH1) expression and thus promoted sorafenib resistance in vitro. Mice experiments also confirmed that miR-31-5p could mediate drug sensitivity in vivo. In addition, low expression of MLH1 was observed in sorafenib-resistant RCC cells and upregulation of MLH1 expression restored the sensitivity of resistant cell lines to sorafenib. Finally, miR-31-5p level in circulating EVs of RCC patients with progressive disease (PD) during sorafenib therapy was higher when compared to that in the pretherapy status. In conclusion, EVs shuttled miR-31-5p can transfer resistance information from sorafenib-resistant cells to sensitive cells by directly targeting MLH1, and thus magnify the drug resistance information to the whole tumor. Furthermore, miR-31-5p and MLH1 could be promising predictive biomarkers and therapeutic targets to prevent sorafenib resistance.     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

Adult Renal Cell Carcinoma: A Review of Established Entities from Morphology to Molecular Genetics

According to the current World Health Organization (WHO), renal cell carcinomas (RCCs) that primarily affect adults are classified into 8 major subtypes. Additional emerging entities in renal neoplasia have also been recently recognized and these are discussed in further detail by Mehra et al (Emerging Entities in Renal Neoplasia, Surgical Pathology Clinics, 2015, Volume 8, Issue 4). In most cases, the diagnosis of a RCC subtype can be based on morphologic criteria, but in some circumstances the use of ancillary studies can aid in the diagnosis. This review discusses the morphologic, genetic, and molecular findings in RCCs previously recognized by the WHO, and provides clues to distinction from each other and some of the newer subtypes of RCC. As prognosis and therapeutic options vary for the different subtypes of RCC, accurate pathologic distinction is critical for patient care.     

ArcCHECK系统在食管癌螺旋断层放疗计划验证中的应用

目的 探讨ArcCHECK系统在食管癌断层治疗旋转照射和固定野照射计划验证中的应用,总结相关经验。方法 对32例不同部位食管癌分别制作Helical旋转照射和Direct固定野照射验证计划,并通过ArcCHECK测量、分析,对比验证结果通过率。分析靶体积与计划验证通过率的相关性。将靶体积较小的治疗验证计划分别放在ArcCHECK模体中心和外周探测点处,分析验证通过率差异。结果 Helical计划验证通过率高于Direct计划(P<0.01),其靶体积与验证通过率的相关系数分别为-0.364和-0.042,P值分别为0.041和0.819。Helical计划采用3%/2mm标准时,高剂量区放在模体中心和外周探测点处测得的通过率不同(P=0.005),后者通过率更高;采用3%/3mm标准时与Direct计划的3%/3m、3%/2mm标准的相近(P均>0.05)。结论 Helical计划验证通过率普遍高于Direct计划,原因可能与ArcCHECK探测器的角度响应以及因更多参考点受到低剂量辐射而未参与计算有关,另外还可能跟Direct计划对断层治疗剂量控制系统要求更高有关。在Helical验证计划中,当采用3%/3mm标准时,靶体积越大,验证时出现较低通过率的可能性增加,但相关系数较低。验证计划的高剂量区位于模体中心或者探测点处都可以实现计划验证,综合考量建议放在模体等中心处。     

CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.     

食管癌根治性放疗剂量研究进展

同步放化疗是不可手术局部晚期食管癌的标准治疗模式,国际推荐根治性放疗剂量为50.0~50.4Gy,但中国食管癌与西方国家在病理类型、生物学行为等方面大有不同,行根治性放疗剂量仍倾向于60Gy。增加放疗剂量能否带来生存获益成为临床亟待解决的问题。有研究认为高剂量放疗可提高局控率、改善生存,但也有研究认为提高剂量未能带来生存获益,且可增加不良反应事件发生率。因此,本文就食管癌根治性放疗剂量对预后的影响进行探讨,并通过放化疗后疗效评估对放疗剂量做出适当调整,以期达个体化放疗。     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.