Optimizing Ovarian Function Preservation for Young Cervical Cancer Patients After Oophoropexy: A Dosimetric and Radiobiological Comparison of Three Radiotherapy Techniques (IMPT, TOMO, and VMAT)

Purpose: To systematically compare the dosimetric performance and radiobiological outcomes of intensity-modulated proton therapy (IMPT), helical tomotherapy (TOMO), and volumetric modulated arc therapy (VMAT) for ovarian function preservation in young cervical cancer patients following radical hysterectomy with bilateral ovarian transposition. Methods: Ten premenopausal cervical cancer patients who received postoperative pelvic radiotherapy following bilateral ovarian transposition were retrospectively enrolled. Three treatment plans (IMPT, TOMO, VMAT) were designed for each patient with a uniform prescription of 45 Gy in 25 fractions. IMPT plans incorporated robust optimization accounting for setup uncertainty (5 mm) and range uncertainty (3.5%). Dosimetric parameters evaluated included target coverage (\((V_{100%})\)), homogeneity index (HI), ovarian mean dose (\((D_{mean})\)) and maximum dose (\((D_{max})\)), and dose-volume metrics for organs at risk (OARs: rectum, bladder, small intestine, sigmoid, femoral heads). Radiobiological analyses included equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and excess absolute risk (EAR) of secondary malignancies using Schneider's mechanistic model. Results: All three techniques achieved clinically acceptable target coverage. IMPT demonstrated superior dose homogeneity (HI: \((0.02\pm0.01)\) vs. 0.04–0.06 for photon techniques, \((p<0.05)\)). For ovarian sparing, IMPT significantly reduced \((D_{mean})\) by approximately 95% compared to photon-based techniques (0.11–0.35 Gy vs. 4.44–5.24 Gy, \((p \le 0.002)\)) and substantially minimized low-dose exposure (\((V_{5Gy}<0.4)\) cc vs. 2.86–7.68 cc, \((p \le 0.018)\)). Both IMPT and TOMO achieved significantly lower maximum dose (\((D_{max})\)) to the rectum, bladder, and small intestine than VMAT (\((p<0.05)\)). IMPT reduced small intestine \((V_{35Gy})\) by approximately 30% and mean bladder dose by 35% compared to photon techniques. NTCP analysis demonstrated that IMPT significantly reduced the risk of late toxicity to the small intestine, rectum, and bladder compared to both TOMO and VMAT (\((p<0.05)\)), while comparable femoral head protection was observed between IMPT and VMAT, both significantly superior to TOMO (\((p<0.05)\)). EAR modeling revealed that IMPT minimized bladder cancer risk (\((p = 0.002)\)), whereas VMAT achieved the lowest rectal cancer risk (\((p \le 0.006)\). IMPT also reduced integral dose to normal tissue by 54% compared to photon modalities. VMAT exhibited the shortest beam-on time (\((2.20\pm0.05)\) min vs. TOMO \((8.18\pm0.99)\) min, \((p<0.001)\)). Conclusion: IMPT demonstrated unparalleled ovarian dose reduction and superior protection against radiation-induced secondary cancers for most pelvic OARs, establishing it as the optimal technique for ovarian function preservation when available. VMAT offers superior treatment efficiency but requires stringent ovarian dose constraints. TOMO provides comparable high-dose OAR protection to IMPT but is limited in minimizing low-dose ovarian exposure. Technique selection should be individualized based on available resources and patient priorities, with IMPT strongly recommended for young patients prioritizing long-term ovarian function.