Yilmaz Melek Tugce, Yedekci Fazli Yagiz, Mohammadipour Sepideh, Kivanc Huseyin, Cengiz Mustafa, Cifci Gokcen, Kertmen Neyran, Yazici Gozde
Radiation Oncology, Hacettepe University Medical School, Ankara, TUR.
Radiation Oncology, Hacettepe University, Ankara, TUR.
Cureus. 2025 Jun 5;17(6):e85383. doi: 10.7759/cureus.85383. eCollection 2025 Jun.
Lattice radiotherapy (LRT), a modern form of spatially fractionated radiation therapy, introduces a novel therapeutic strategy by delivering high-dose vertices interspersed within the gross tumor volume (GTV), leveraging both direct cytotoxicity and immune-mediated effects. While this technique has been explored in extracranial malignancies, its clinical application in intracranial tumors remains scarce. This study presents a preliminary case series assessing the feasibility, safety, and early clinical outcomes of LRT delivered via the gyroscopic radiosurgery platform ZAP-X® (ZAP Surgical Systems, Inc., San Carlos, USA) in patients with recurrent glioblastoma multiforme (GBM) who had already undergone multiple courses of radiotherapy. Between December 2024 and February 2025, four patients with histologically confirmed GBM received single-fraction LRT with a prescribed dose of 20 Gy to each lattice vertex. Patient-specific lattice geometries were generated using a custom Python-based software tool, ensuring high-dose spheres were fully confined within the GTV and spaced to achieve a peak-to-valley dose ratio of 4. Treatment plans were created on the ZAP-X system using multi-isocenter targeting and optimized to deliver a mean GTV dose exceeding 5 Gy. The tumor volumes of the four presented cases were 186 cc, 68 cc, 75 cc, and 293 cc. Treatment delivery times ranged between 44 and 46 minutes. All patients were evaluated clinically and radiologically at 1 and 3 months post-treatment. LRT was successfully delivered in all cases with favorable treatment tolerability and no acute neurotoxicity. Early imaging revealed radiological response or disease stabilization in three patients. One patient demonstrated significant cystic transformation and maintained stable neurological status; another exhibited partial response prior to disease progression at a distant intracranial site. The third patient remained clinically and radiologically stable without requiring systemic therapy. The fourth patient, who had a poor baseline status, experienced local progression and was hospitalized due to aspiration pneumonia. Across the cohort, steroid requirements were stable or reduced post-treatment. These early findings suggest that ZAP-X-based LRT is a feasible and well-tolerated reirradiation option in heavily pretreated GBM patients. By integrating high-dose and low-dose regions within the tumor, LRT may stimulate immunologic effects and improve local control without increasing toxicity. Although limited by small sample size and short follow-up, this study supports the potential of LRT as a palliative strategy and sets the foundation for future prospective trials exploring its clinical efficacy and immunomodulatory role in neuro-oncology.
点阵放射治疗（LRT）是空间分割放射治疗的一种现代形式，它通过在大体肿瘤体积（GTV）内散布高剂量顶点，引入了一种新的治疗策略，利用直接细胞毒性和免疫介导效应。虽然该技术已在颅外恶性肿瘤中进行了探索，但其在颅内肿瘤中的临床应用仍然很少。本研究呈现了一个初步病例系列，评估了通过陀螺式放射外科平台ZAP-X®（美国圣卡洛斯ZAP Surgical Systems公司）对已接受多程放疗的复发性多形性胶质母细胞瘤（GBM）患者进行LRT治疗的可行性、安全性和早期临床结果。在2024年12月至2025年2月期间，4例经组织学确诊为GBM的患者接受了单分割LRT治疗，每个点阵顶点的处方剂量为20 Gy。使用基于Python的定制软件工具生成患者特异性的点阵几何形状，确保高剂量球体完全局限在GTV内，并进行间隔以实现峰谷剂量比为4。在ZAP-X系统上使用多等中心靶向创建治疗计划，并进行优化以提供超过5 Gy的平均GTV剂量。所呈现的4例病例的肿瘤体积分别为186 cc、68 cc、75 cc和293 cc。治疗交付时间在44至46分钟之间。所有患者在治疗后1个月和3个月进行了临床和影像学评估。所有病例均成功进行了LRT治疗，治疗耐受性良好，无急性神经毒性。早期影像学显示3例患者有放射学反应或疾病稳定。1例患者出现明显的囊性变并保持神经状态稳定；另1例在远处颅内部位疾病进展前表现出部分缓解。第3例患者在临床和影像学上保持稳定，无需全身治疗。第4例患者基线状态较差，出现局部进展，并因吸入性肺炎住院。在整个队列中，治疗后类固醇需求稳定或减少。这些早期发现表明基于ZAP-X的LRT是对经过大量预处理的GBM患者可行且耐受性良好的再照射选择。通过在肿瘤内整合高剂量和低剂量区域，LRT可能刺激免疫效应并改善局部控制而不增加毒性。尽管受样本量小和随访时间短的限制，本研究支持LRT作为一种姑息治疗策略的潜力，并为未来探索其在神经肿瘤学中的临床疗效和免疫调节作用的前瞻性试验奠定了基础。
