Spatially fractionated radiation therapy (SFRT) has shown promise in generating high tumor response and local control in the treatment of various palliative and locally advanced bulky tumors. SFRT has not yet been studied systematically in cancer of the cervix. Here we report the first series of patients receiving SFRT for advanced/bulky cervical cancer. Ten patients with far-advanced bulky cervical cancer, stage IIIB–IVA (seven squamous cell and three adeno/adenosquamous carcinomas) received lattice radiation therapy (LRT), a variant of SFRT. The LRT regimen consisted of a dose of 24 Gy in three fractions, given to an average of five high-dose spheres within the gross tumor volume (GTV). The dose in the peripheral GTV was limited to 9 Gy in three fractions, using the volumetric modulated arc therapy (VMAT) technique. LRT was followed subsequently by conventionally fractionated external beam irradiation to 44.28 Gy (range: 39.60–45.00 Gy in 1.8 Gy fractions). All patients received concurrent cisplatin chemotherapy. Tumor response was assessed clinically, by morphological imaging (CT, MRI) and ¹⁸FDG PET/CT. Tumor control and survival rates were estimated using Kaplan-Meier analysis. All patients had local control at a median follow-up of 16 months (1–77). The two-year disease-specific survival rate was 53.3%. All cancer deaths were due to metastatic failure with local control maintained. Among the three patients who died of disease, all had adeno- or adenosquamous carcinoma histology, and no deaths from disease occurred among the patients with squamous cell carcinoma (P = 0.010). There were no grade ≥3 short-term or long-term treatment-related complications. Intra-treatment morphological tumor regression was highly variable (mean: 54%, range: 6–91%). After therapy, the complete metabolic response was 88.9% (8/9), and one patient out of the nine patients with post-treatment PET-CT had partial response (11.1%). Our preliminary data suggest that LRT-based SFRT is well tolerated in patients with far-advanced bulky cervical cancer and results in favorable tumor responses and high local control. These observations confirm prior reports of favorable tumor control and toxicity outcomes with SFRT in other advanced/bulky malignancies. Our findings are corroborated by high molecular-imaging-based tumor response. These encouraging hypothesis-generating results require cautious interpretation and confirmation with larger patient cohorts, preferably through a multi-institutional controlled randomized clinical trial.

在各种姑息性和局部晚期大体积肿瘤的治疗中，空间分割放射疗法（SFRT）在产生高肿瘤应答和局部控制方面已显示出希望。SFRT尚未在宫颈癌中进行系统研究。在这里，我们报告了第一批接受SFRT治疗的晚期/大块宫颈癌患者。十例IIIB-IVA期（7个鳞状细胞癌和3个腺/腺鳞癌）晚期大块状宫颈癌患者接受了晶格放射疗法（LRT）（SFRT的一种）。LRT方案由三部分组成的24 Gy剂量组成，平均总肿瘤体积（GTV）内有五个高剂量球体。使用体积调制弧光治疗（VMAT）技术，外周GTV的剂量分为三个部分，限制为9 Gy。在进行LRT手术后，通常进行分次的外部束辐照至44.28 Gy（范围：39.60–45.00 Gy（1.8 Gy分数））。所有患者同时接受顺铂化疗。临床上通过形态学成像（CT，MRI）评估肿瘤反应¹⁸ FDG PET / CT。使用Kaplan-Meier分析评估肿瘤的控制和生存率。所有患者均接受局部控制，平均随访16个月（1–77）。两年特定疾病生存率为53.3％。所有癌症死亡均归因于转移失败并维持局部控制。在三例死于疾病的患者中，所有患者均具有腺鳞癌或腺鳞癌的组织学特征，鳞状细胞癌患者中没有因疾病死亡（P= 0.010）。没有短期或长期治疗相关的≥3级并发症。术中形态学肿瘤消退变化很大（平均：54％，范围：6-91％）。治疗后，完全代谢反应为88.9％（8/9），治疗后的9例PET-CT患者中有1例有部分反应（11.1％）。我们的初步数据表明，基于LRT的SFRT在晚期大体积宫颈癌患者中耐受性良好，并导致良好的肿瘤反应和高度的局部控制。这些观察结果证实了先前报道的SFRT在其他晚期/大块恶性肿瘤中具有良好的肿瘤控制和毒性结果。基于高分子成像的肿瘤反应证实了我们的发现。