Innovative Cancer Institute, Miami, Florida.
Department of Radiation Oncology, University of Washington School of Medline, Seattle, Washington.
Radiat Res. 2020 Dec 1;194(6):724-736. doi: 10.1667/RADE-20-00038.1.
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.
立体定向分次放射治疗（SFRT）在治疗各种姑息性和局部晚期大块肿瘤方面显示出提高肿瘤反应和局部控制的潜力。SFRT 尚未在宫颈癌的治疗中得到系统研究。在这里，我们报告了第一批接受 SFRT 治疗晚期/大块宫颈癌的患者。10 例晚期大块宫颈癌患者，IIIb-IVa 期（7 例鳞状细胞癌和 3 例腺癌/腺鳞癌）接受了格放射治疗（LRT），这是 SFRT 的一种变体。LRT 方案包括在 3 次分割中给予 24 Gy 的剂量，在大体肿瘤体积（GTV）内给予平均 5 个高剂量球。外周 GTV 的剂量限制在 3 次分割中为 9 Gy，使用容积调制弧形治疗（VMAT）技术。随后，LRT 后采用常规分割外照射至 44.28 Gy（范围：39.60-45.00 Gy，1.8 Gy 分次）。所有患者均接受顺铂同期化疗。通过临床、形态学成像（CT、MRI）和 18FDG PET/CT 评估肿瘤反应。采用 Kaplan-Meier 分析估计肿瘤控制和生存率。所有患者在中位随访 16 个月（1-77 个月）时均获得局部控制。两年疾病特异性生存率为 53.3%。所有癌症死亡均归因于转移性失败，局部控制得到维持。在死于疾病的 3 名患者中，所有患者均为腺癌或腺鳞癌组织学类型，而鳞状细胞癌患者无一例死于疾病（P = 0.010）。无≥3 级短期或长期治疗相关并发症。治疗过程中肿瘤形态学回归高度可变（平均：54%，范围：6-91%）。治疗后，完全代谢反应率为 88.9%（8/9），9 名患者中有 1 名患者在 PET-CT 治疗后有部分反应（11.1%）。我们的初步数据表明，基于 LRT 的 SFRT 在晚期大块宫颈癌患者中耐受性良好，可获得良好的肿瘤反应和高局部控制率。这些观察结果证实了 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的先前报告。我们的发现得到了高基于分子影像学的肿瘤反应的支持。这些令人鼓舞的产生假设的结果需要谨慎解释，并通过更大的患者队列进行确认，最好是通过多机构对照随机临床试验。
