International journal of radiation oncology, biology, physics · 2026
Toward Optimal Fractionation Schemes in Nonuniform Radiation Therapy: Exploiting Helical Tomotherapy's Thread Effect for Gynecological Cancer Treatment.
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Luo Huanli, Yang Mengqi, Li Jianfeng, Qiu Tao, Hu Wenyou, Song Yunrui, Wang Tian, Peng Haiyan, Yang Xin, Feng Bin, Chen Liyuan, Tan Liang, Liang Bo, Wang Ying, Jin Fu
Аннотация
PURPOSE: This study aimed to optimize dose fractionation for helical tomotherapy-based spatially fractionated radiation therapy (HT-SFRT) in gynecologic cancers by exploiting the "thread effect" to induce cohort effects.
METHODS AND MATERIALS: HT-SFRT plans with varying parameters (pitch: 0.3-0.5; field width: 2.512 and 5.048 cm; modulation factor: 1.0-4.0) were applied to HeLa cells to identify the optimal configuration maximizing the peak-to-valley dose ratio. The cohort effect threshold was determined through quantification of DNA damage (γ-H2AX) and cell viability. Clinical validation involved 45 patients with gynecologic cancer, comparing 3 treatment approaches: conventional HT, stereotactic body radiation therapy, and SFRT (3 and 4 fractions). Comprehensive dosimetric analysis included evaluation of physical doses, biologically effective doses, tumor control probability, and normal tissue complication probability (NTCP) using the universal survival curve and Lyman-Kutcher-Burman models.
RESULTS: Optimized HT-SFRT parameters (field width = 5.048 cm; pitch = 0.5; modulation factor = 2.0) achieved a peak-to-valley dose ratio of 1.15 at 10 cm off-axis. The 8 Gy/fraction dose threshold induced significant γ-H2AX expression and reduced cell viability by 15.41% (P < .05), establishing the cohort effect criterion. Clinically, the 32 Gy/4 fractions SFRT regimen demonstrated approximate tumor control (tumor control probability: 99.34% vs 100%) to conventional HT (50 Gy/25 fractions), whereas offering superior therapeutic advantages: (1) 84% reduction in treatment duration (4 vs 25 days); (2) significantly lower NTCP for bladder (6.5 × 10-⁶ % vs 3.6 × 10-⁴ %, P = .05); and (3) 42.9% faster fractional delivery than stereotactic body radiation therapy. Notably, SFRT exhibited elevated NTCP for rectum (3.99% vs 0.10%) and femoral head (0.16%-0.22% vs 2.9 × 10-⁷ %-4.8 × 10-⁷ %) structures.
CONCLUSIONS: The thread effect in HT can be harnessed for SFRT, avoiding traditional mitigation strategies. The optimized HT-SFRT scheme (32 Gy/4 fractions) offers equivalent tumor control, shorter treatment duration, and acceptable normal tissue toxicity, providing a promising alternative for gynecologic cancer radiation therapy. Prospective clinical trials are warranted to validate these findings.
METHODS AND MATERIALS: HT-SFRT plans with varying parameters (pitch: 0.3-0.5; field width: 2.512 and 5.048 cm; modulation factor: 1.0-4.0) were applied to HeLa cells to identify the optimal configuration maximizing the peak-to-valley dose ratio. The cohort effect threshold was determined through quantification of DNA damage (γ-H2AX) and cell viability. Clinical validation involved 45 patients with gynecologic cancer, comparing 3 treatment approaches: conventional HT, stereotactic body radiation therapy, and SFRT (3 and 4 fractions). Comprehensive dosimetric analysis included evaluation of physical doses, biologically effective doses, tumor control probability, and normal tissue complication probability (NTCP) using the universal survival curve and Lyman-Kutcher-Burman models.
RESULTS: Optimized HT-SFRT parameters (field width = 5.048 cm; pitch = 0.5; modulation factor = 2.0) achieved a peak-to-valley dose ratio of 1.15 at 10 cm off-axis. The 8 Gy/fraction dose threshold induced significant γ-H2AX expression and reduced cell viability by 15.41% (P < .05), establishing the cohort effect criterion. Clinically, the 32 Gy/4 fractions SFRT regimen demonstrated approximate tumor control (tumor control probability: 99.34% vs 100%) to conventional HT (50 Gy/25 fractions), whereas offering superior therapeutic advantages: (1) 84% reduction in treatment duration (4 vs 25 days); (2) significantly lower NTCP for bladder (6.5 × 10-⁶ % vs 3.6 × 10-⁴ %, P = .05); and (3) 42.9% faster fractional delivery than stereotactic body radiation therapy. Notably, SFRT exhibited elevated NTCP for rectum (3.99% vs 0.10%) and femoral head (0.16%-0.22% vs 2.9 × 10-⁷ %-4.8 × 10-⁷ %) structures.
CONCLUSIONS: The thread effect in HT can be harnessed for SFRT, avoiding traditional mitigation strategies. The optimized HT-SFRT scheme (32 Gy/4 fractions) offers equivalent tumor control, shorter treatment duration, and acceptable normal tissue toxicity, providing a promising alternative for gynecologic cancer radiation therapy. Prospective clinical trials are warranted to validate these findings.
Предметные рубрики MeSH
HumansFemaleDose Fractionation, RadiationHistonesGenital Neoplasms, FemaleRadiotherapy, Intensity-ModulatedHeLa CellsCell SurvivalUterine Cervical NeoplasmsOrgans at RiskRadiosurgeryDNA DamageRelative Biological EffectivenessRectumRadiotherapy Planning, Computer-AssistedUrinary BladderOvarian NeoplasmsEndometrial Neoplasms