Clinical Application of Proton Beams in the Treatment of Uveal Melanoma: The First Therapies Carried Out in Italy and Preliminary Results (Catana Project)
Clinical Application of Proton Beams in the Treatment of Uveal Melanoma: The First Therapies Carried Out in Italy and Preliminary Results (Catana Project)
复制标题
质子束治疗葡萄膜黑色素瘤的临床应用：在意大利进行的首次治疗及初步结果（Catana项目）
作者：
C. Spatola;G. Privitera;L. Raffaele;V. Salamone;G. Cuttone;P. Cirrone;M. G. Sabini;S. Lo Nigro
背景 意大利第一个质子治疗设施在卡塔尼亚的 INFN-LNS 建成。凭借其能量（62 MeV 质子束），它非常适合治疗浅部肿瘤，例如眼部肿瘤：首先是葡萄膜黑色素瘤（成人最常见的原发性眼内恶性肿瘤），以及其他不太常见的病变，例如脉络膜血管瘤、结膜黑色素瘤和眼睑肿瘤。材料和方法 第一位患者于 2002 年 2 月入组，迄今为止已有 30 名患者接受治疗。所有患者均为局限性葡萄膜黑色素瘤，无全身转移，且具有质子束放射治疗的特定指征：病灶基底直径在5-25毫米之间，厚度不超过15毫米，无完全视网膜脱离或青光眼。根据肿瘤尺寸，小病灶或T1 2例（6%），中型病灶或T2 3例（10%），大病灶或T3 14例（47%），特大病灶或T3 11例（37%）；没有患者出现巩膜外侵犯或 TNM-AJCC 分期系统 T4。在大多数情况下，肿瘤仅浸润脉络膜（14 名患者，47%）或脉络膜加睫状体（14 名患者，47%）。我们还治疗了原始虹膜黑色素瘤，未扩散至睫状体。靶体积定义为肿瘤加上横向和前后2.5mm的安全裕度；如果存在睫状体受累，则该边缘增加至 3 毫米。治疗连续 4 天分 4 次进行，总剂量为 54.5 Gy（单次剂量 13.6 Gy），相当于 60 CGE（钴灰当量；单次剂量 15 CGE），因为相对生物有效性为 1.1。结果 第一次随访计划在治疗结束后 6-8 个月进行，我们的临床终点是局部控制（定义为生长停止或肿瘤缩小）、眼睛保留和良好视功能的维持。截至撰写本文时，我们已获得 13 名患者的初步结果。 9 名患者表现出肿瘤缩小（69%），3 名患者尺寸基本稳定（23%），但几乎所有患者都表现出超声反射率增加（肿瘤控制的替代指标）。讨论和结论文献数据显示，带电粒子疗法在葡萄膜黑色素瘤的治疗中实现了最佳的局部控制（不同系列中约96％，优于斑块疗法[83％至92％]），转移率略好于摘除报告，5年生存率接近90％。我们的初步结果显示几乎所有病例都有肿瘤反应，没有严重的急性或亚急性副作用。因此，我们计划继续我们的治疗程序和剂量处方。
Background The first Italian proton therapy facility was realized in Catania, at the INFN-LNS. With its energy (62 MeV proton beam), it is ideal for the treatment of shallow tumors like those of the ocular region: uveal melanoma, first of all (the most common primary intraocular malignancy of adults) and other less frequent lesions like choroidal hemangioma, conjunctiva melanoma, and eyelid tumors. Material and methods The first patient was enrolled in February 2002, and to date 30 patients have been treated. All patients had a localized uveal melanoma, with no systemic metastases, and had specific indications for proton beam radiation therapy: lesions between 5–25 mm basal diameter, not exceeding 15 mm thickness, absence of total retinal detachment or glaucoma. According to the tumor dimensions, 2 patients had a small lesion or T1 (6%), 3 had a medium-sized lesion or T2 (10%), 14 had a large lesion or T3 (47%), and 11 had an extra-large lesion or T3 (37%); no patient had extrascleral invasion or T4 of the TNM-AJCC Staging System. In most cases, the tumor infiltrated only the choroid (14 patients, 47%) or the choroid plus the ciliary body (14 patients, 47%). We also treated a primitive iris melanoma, without diffusion to the ciliary body. The target volume was defined as the tumor plus a safety margin of 2.5 mm, laterally and antero-posteriorly; this margin was increased to 3 mm if ciliary body involvement was present. The treatment was carried out in 4 fractions on 4 consecutive days to a total dose of 54.5 Gy (single fraction 13.6 Gy), which corresponds to 60 CGE (Cobalt Gray Equivalent; single fraction 15 CGE), because the relative biological effectiveness is 1.1. Results The first follow-up is planned at 6–8 months after the end of the treatment, and our clinical end points are local control (defined as cessation of growth or tumor shrinkage), eye retention, and maintenance of a good visual function. At the time of this writing, we had preliminary results from 13 patients. Nine patients showed tumor shrinkage (69%), 3 a substantially stable dimension (23%), but almost all patients presented an increased ultrasound reflectivity (a surrogate for tumor control). Discussion and conclusions The literature data show that charged particle therapy has allowed an optimal local control in the treatment of uveal melanomas (about 96% in the different series, superior to that obtained with plaquetherapy [between 83% and 92%]), a metastatic rate slightly better than enucleation reports, and a survival rate of almost 90% at 5 years. Our preliminary results show a tumor response in almost all cases, with no major acute or subacute side effects. We thus plan to continue with our treatment procedures and our dose prescription.