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Integrating a Ripple Filter into Pencil Beam Scanning Proton Therapy for Breast Cancer: from Dosimetric Feasibility to Acute Toxicity Assessment
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DOI：10.1186/s12885-026-16601-2.png)
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Abstract
En 中文
Pencil beam scanning (PBS) proton therapy (PT) offers superior dosimetric advantages for breast cancer treatment. However, synchrotron-based facilities frequently encounter throughput limitations due to slow energy layer switching, particularly problematic for superficial targets requiring numerous energy layers. Although ripple filters (RiFis) can mitigate this constraint by broadening the Bragg peak, their application in breast cancer PT remains unexplored. This study comprehensively investigates the feasibility, efficiency gains, linear energy transfer (LET) characteristics, and clinical safety of integrating a RiFi into PBS PT for breast cancer. We conducted a two-phase investigation beginning with a dosimetric planning study and proceeding to clinical validation. In phase Ⅰ, we generated paired treatment plans (RiFi vs. non-RiFi) for 21 patients (11 breast-conserving surgery [BCS] and 10 modified radical mastectomy [MRM]) to compare target coverage, organ-at-risk (OAR) sparing, dose-averaged LET (LETd) distributions, and number of energy layers. In phase Ⅱ, we conducted a retrospective analysis of 99 BCS patients treated between January and December 2025, employing 1:1 multivariate matching to control for treatment volume and prescription dose, resulting in 37 well-balanced pairs. Dose-volume and LETd parameters, Acute toxicities and treatment delivery time were compared between matched groups. In phase Ⅰ dosimetric study, RiFi plans maintained robust target coverage (V95). However, the broadened beam introduced slight but statistically significant increments in doses to OARs. For BCS patients, the mean ipsilateral lung dose and mean heart dose increased by 0.13 Gy(RBE) (95% confidence interval [CI]: 0.08–0.28 Gy(RBE), p < .001) and 0.04 Gy(RBE) (95% CI: 0.02–0.06 Gy(RBE), p = .006), respectively. For MRM patients, the mean ipsilateral lung dose and mean heart dose increased by 0.79 Gy(RBE) (95% CI: 0.46–1.10 Gy(RBE), p = .002) and 0.08 Gy(RBE) (95% CI: 0.04–0.19 Gy(RBE), p = .009), respectively. Conversely, the RiFi significantly decreased LETd by 0.15–0.65 keV/µm to skin and distal OARs. Phase Ⅱ clinical validation demonstrated similar LETd reduction and no significant differences in the incidence or severity of acute radiation-induced dermatitis or esophagitis between groups. RiFi integration significantly enhanced treatment efficiency, reducing actual beam delivery time by approximately 20%. Integrating a RiFi into breast cancer PBS PT effectively improves delivery efficiency and mitigates distal high-LETd exposure, albeit at the cost of slight increments in low-dose exposure to distal OARs. Clinical data confirm this dosimetric change does not compromise acute safety for BCS patients. These findings suggest that the RiFi is a feasible option for improving treatment delivery efficiency in synchrotron-based PT systems.
Keywords:
Breast cancer
Proton therapy
Ripple filter
Acute toxicity
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