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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.