Aims

Sacral chordomas are locally aggressive, radio-resistant tumours. Proton therapy has the potential to deliver high radiation doses, which may improve the therapeutic ratio when compared with conventional radiotherapy. We assessed tumour control and radiation-induced toxicity in a cohort of sacral chordoma patients treated with definitive or postoperative pencil beam scanning proton therapy.

Methods and materials

Sixty patients with histologically proven sacral chordoma treated between November 1997 and October 2018 at the Paul Scherrer Institute with postoperative (n = 50) or definitive proton therapy (n = 10) were retrospectively analysed. Only 10 (17%) patients received combined photon radiotherapy and proton therapy. Survival rates were calculated using the Kaplan–Meier actuarial method. The Log-rank test was used to compare different functions for local control, freedom from distant recurrence and overall survival. Acute and late toxicity were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Results

The median follow-up was 48 months (range 4–186). Local recurrence occurred in 20 (33%) patients. The 4-year local control, freedom from distant recurrence and overall survival rates were 77%, 89% and 85%, respectively. On univariate analysis, subtotal resection/biopsy (P = 0.02), tumour extension restricted to bone (P = 0.01) and gross tumour volume >130 ml (P = 0.04) were significant predictors for local recurrence. On multivariate analysis, tumour extension restricted to bone (P = 0.004) and gross total resection (P = 0.02) remained independent favourable prognostic factors for local recurrence. Twenty-four (40%), 28 (47%) and eight (11%) patients experienced acute grade 1, 2 and 3 toxicities, respectively. The 4-year late toxicity-free survival was 91%. Two patients developed secondary malignancies to the bladder 3–7 years after proton therapy.

Conclusions

Our data indicate that pencil beam scanning proton therapy for sacral chordomas is both safe and effective. Gross total resection, tumour volume <130 ml and tumour restricted to the bone are favourable prognostic factors for local tumour control.

中文翻译：

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铅笔束扫描质子治疗骶骨脊索瘤患者的临床疗效

宗旨

骶骨脊索瘤是局部侵袭性、抗辐射的肿瘤。质子治疗具有提供高辐射剂量的潜力，与传统放射治疗相比，这可能会提高治疗率。我们评估了一组接受根治性或术后笔形束扫描质子治疗的骶骨脊索瘤患者的肿瘤控制和放射诱导的毒性。

方法和材料

回顾性分析了1997 年 11 月至 2018 年 10 月在 Paul Scherrer 研究所接受术后（n = 50）或确定性质子治疗（n = 10）治疗的60 名经组织学证实的骶骨脊索瘤患者。只有 10 (17%) 名患者接受了联合光子放疗和质子治疗。使用 Kaplan-Meier 精算方法计算存活率。对数秩检验用于比较局部控制、无远处复发和总生存的不同功能。根据不良事件通用术语标准 (CTCAE) v5.0 评估急性和晚期毒性。

结果

中位随访时间为 48 个月（范围 4-186）。20 名 (33%) 患者发生局部复发。4 年局部控制率、无远处复发率和总生存率分别为 77%、89% 和 85%。在单变量分析中，次全切除/活检 ( P = 0.02)、肿瘤局限于骨骼 ( P = 0.01) 和总肿瘤体积 > 130 ml ( P = 0.04) 是局部复发的重要预测因素。在多变量分析中，肿瘤扩展限于骨 ( P = 0.004) 和总切除 ( P= 0.02) 仍然是局部复发的独立有利预后因素。分别有 24 名 (40%)、28 名 (47%) 和 8 名 (11%) 患者出现急性 1、2 和 3 级毒性。4 年晚期无毒性生存率为 91%。两名患者在质子治疗后 3-7 年发展为膀胱继发性恶性肿瘤。

结论

我们的数据表明，骶骨脊索瘤的笔形束扫描质子治疗既安全又有效。大体全切除、肿瘤体积 <130 ml 和肿瘤局限于骨骼是局部肿瘤控制的有利预后因素。