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轴向骨和软组织肉瘤碳离子放疗的结果和毒性。

Outcome and Toxicity of Carbon Ion Radiotherapy for Axial Bone and Soft Tissue Sarcomas.

机构信息

National Center of Oncological Hadrontherapy (Fondazione CNAO), Pavia, Italy.

Advanced Radiation Oncology Department, Cancer Care Center, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy.

出版信息

Anticancer Res. 2020 May;40(5):2853-2859. doi: 10.21873/anticanres.14260.

Abstract

BACKGROUND/AIM: Definitive radiotherapy for bone and soft tissues sarcomas benefits patients deemed unfit for surgery; poor outcomes have been reported with conventional photons, while interesting preliminary results have been described with particle in single-Institution experiences. The aim of the study was to retrospectively evaluate preliminary results of carbon ion radiotherapy (CIRT) in patients with axial bone and soft tissue sarcomas (BSTS) treated with curative intent at the National Center for Oncological Hadrontherapy (CNAO).

PATIENTS AND METHODS

From January 2013 to September 2018, 54 patients with axial BSTS were treated with CIRT at CNAO. Their median age was 50 years (range=19-79 years), males/females=1.4:1. Tumor site was the pelvis in 50% of cases (n=27), thoracic region in 24% (n=13), cervical spine in 15% (n=8) and lumbar in 11% (n=6). A total of 76% (n=41) of patients had primary disease, while 24% (n=13) had recurrent disease. Before CIRT, surgery was performed in 47% of cases, including positive margins (R1) in 8 patients, and macroscopic residual disease (R2) in 17. Histological subtypes were mainly represented by chondrosarcomas in 39% (n=21) of patients and osteosarcomas in 24% (n=13). Pre-treatment chemotherapy was administered in 40% of cases (n=22); no patient received previous radiotherapy. All treatments were performed with active scanning CIRT for a median total dose of 73.6 Gy (range=70.4-76.8 Gy), in 16 fractions (4 fractions per week).

RESULTS

Median follow-up was 24 months (range=4-61 months). Four patients were lost to follow-up. Acute toxicities were mild, no >G2 event was reported and no treatment interruption was required. For late toxicity, only G3 neuropathy was detected in 4% of cases (n=2). With a median time to local progression of 13 months (3-35), 15 local failures were observed, resulting in 2- and 3-year local control rates of 67.4% for both. Distant progression occurred in 12 patients, with 1-year progression-free survival (PFS) rate of 97.5%; 2- and 3-year rates were 92.2%. Fifteen patients died resulting in 1- 2- and 3-years overall survival (OS) rates of 87.1%, 75.4% and 64%, respectively. At log-rank test, gross total volume (GTV) >1,000 ml was found to be predictive of local failure (p=0.04), pre-treatment chemotherapy was found to be significantly related to PFS and OS (p=0.02 and p=0.016); also, recurrent disease and distant progression were significantly related to OS (p=0.019 and p=0.0013). Cox proportional-hazards model confirmed that GTV >1,000 ml was related to worse local control (p=0.0010).

CONCLUSION

CIRT for axial BSTS resulted in mild toxicity, showing promising results in terms of clinical outcomes. A longer follow-up is warranted.

摘要

背景/目的:对于不适合手术的骨和软组织肉瘤患者,确定性放疗是有益的;虽然在单机构经验中描述了有趣的初步结果,但常规光子治疗的结果较差。本研究的目的是回顾性评估国立癌症质子治疗中心(CNAO)以治愈为目的对轴向骨和软组织肉瘤(BSTS)患者使用碳离子放疗(CIRT)的初步结果。

患者和方法

从 2013 年 1 月至 2018 年 9 月,54 例轴向 BSTS 患者在 CNAO 接受 CIRT 治疗。他们的中位年龄为 50 岁(范围=19-79 岁),男性/女性=1.4:1。肿瘤部位为骨盆 50%(n=27)、胸部 24%(n=13)、颈椎 15%(n=8)和腰椎 11%(n=6)。76%(n=41)的患者为原发性疾病,24%(n=13)为复发性疾病。在 CIRT 之前,47%的患者接受了手术,包括 8 例患者的边缘阳性(R1)和 17 例患者的肉眼残留疾病(R2)。组织学亚型主要由软骨肉瘤(n=21,占 39%)和骨肉瘤(n=13,占 24%)代表。40%的患者接受了术前化疗(n=22);无患者接受过放疗。所有治疗均采用主动扫描 CIRT 进行,总剂量中位数为 73.6Gy(范围=70.4-76.8Gy),共 16 个分次(每周 4 个分次)。

结果

中位随访时间为 24 个月(范围=4-61 个月)。4 例患者失访。急性毒性轻微,无> G2 级事件发生,无需中断治疗。对于晚期毒性,仅 4%的病例(n=2)检测到 G3 神经病变。局部进展的中位时间为 13 个月(3-35),观察到 15 例局部失败,导致 2 年和 3 年局部控制率分别为 67.4%和 67.4%。12 例患者发生远处进展,1 年无进展生存率(PFS)为 97.5%;2 年和 3 年的 PFS 率分别为 92.2%。15 例患者死亡,导致 1 年、2 年和 3 年的总生存率(OS)分别为 87.1%、75.4%和 64%。对数秩检验显示,大体肿瘤体积(GTV)>1000ml 与局部失败相关(p=0.04),术前化疗与 PFS 和 OS 显著相关(p=0.02 和 p=0.016);此外,复发性疾病和远处进展与 OS 显著相关(p=0.019 和 p=0.0013)。Cox 比例风险模型证实 GTV>1000ml 与局部控制不良相关(p=0.0010)。

结论

轴向 BSTS 的 CIRT 导致轻微的毒性,在临床结果方面显示出有希望的结果。需要更长时间的随访。

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