Proton and carbon ions radiotherapy in skull base chordomas: a prospective study based on a dual particle and a patient-customized treatment strategy.
- 作者列表："Iannalfi A","D'Ippolito E","Riva G","Molinelli S","Gandini S","Viselner G","Fiore MR","Vischioni B","Vitolo V","Bonora M","Ronchi S","Petrucci R","Barcellini A","Mirandola A","Russo S","Vai A","Mastella E","Magro G","Maestri D","Ciocca M","Preda L","Valvo F","Orecchia R
BACKGROUND:The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS) and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion therapy (CIRT). METHODS:We prospectively collected and analyzed data of 135 patients treated between 11/2011 and 12/2018. Total prescription dose in PT group (70 patients) and CIRT group (65 patients) was 74 Gy(RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. RESULTS:After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. 5-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, Gross Tumor Volume (GTV), optic pathways and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity ≥ grade 3 was reported in 11% of patients. CONCLUSIONS:Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways and/or brainstem compression and target coverage were independent prognostic factors for LC.
背景: 本研究的目的是评估局部控制 (LC) 、总生存期 (OS) 的结果和毒性特征，以便更好地确定影响质子治疗 (PT) 和碳离子治疗 (CIRT) 颅底脊索瘤临床结局的因素。 方法: 我们前瞻性地收集和分析了 135 例在 11/2011 和 12/2018 之间接受治疗的患者的数据。PT 组 (70 例) 和 CIRT 组 (65 例) 的总处方剂量为 74 Gy (RBE) 分 37 次给药，70.4 Gy (RBE) 分 16 次给药, 分别 (不良患者中的 CIRT)。采用 Kaplan-Meier 法评价 LC 和 OS。进行单变量和多变量分析，以确定临床结局的预后因素。 结果: 中位随访 44 (范围，6-87) 个月后，CIRT 组和 PT 组分别观察到 14 (21%) 和 8 (11%) 个局部失败。CIRT 队列的 5 年 LC 率为 71%，PT 队列为 84%。CIRT 和 PT 组的估计 5 年 OS 率分别为 82% 和 83%。在多变量分析中，大体肿瘤体积 (GTV) 、视路和/或脑干压缩和剂量覆盖是局部失败风险的独立预后因素。11% 的患者报告了 ≥ 3 级的高发生率毒性。 结论: 粒子放射治疗是治疗颅底脊索瘤的有效方法，其晚期毒性尚可。GTV 、视路和/或脑干压迫和靶区覆盖是 LC 的独立预后因素。
METHODS:BACKGROUND:Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. METHODS:A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients' lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. RESULTS:A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients.
METHODS::Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
METHODS:PURPOSE:The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities. METHODS:We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients. RESULTS:A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively (P = .007), and 5-year event-free survival (EFS) was 51% versus 58% (P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% (P < .001), and 5-year EFS was 36% versus 56% (P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS (P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS (P = .263; HR, 1.312). CONCLUSION:In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.