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Proton beam therapy for head and neck cancers traditionally employs a fixed relative biological effectiveness (RBE) of 1.1, which may underestimate actual biological effects in critical structures. This study evaluates how Linear Energy Transfer (LET) optimization could potentially prevent radiation-induced brachial plexopathy (RIBP). (1) Case presentation: A 65-year-old male with stage IVA p16-positive oropharyngeal squamous cell carcinoma received pencil-beam-scanning intensity-modulated proton therapy with concurrent cisplatin. Due to a right level 4 neck node, the high-risk target volume overlapped with the brachial plexus, resulting in a D0.1cc of 70.3 Gy (RBE = 1.1). Four years post-treatment, the patient developed progressive right upper extremity paresthesia, weakness, and dysesthesia. Electromyography revealed myokymia consistent with brachial plexopathy, while MRI showed hyperintensity of the right brachial plexus corresponding to the radiation field. Conservative treatment with pentoxifylline, gabapentin, and physical therapy improved his symptoms. (2) Methods: The original treatment plan was retrospectively analyzed using Monte Carlo dose algorithms and LET-dependent RBE models from McMahon and McNamara. An LET-optimized plan was created to limit LET_d to 2.0 keV/µm in the brachial plexus. (3) Results: The relative biological equivalent (RBE) dose to 0.1cc of the brachial plexus was 77.8 Gy (CGE RBE), exceeding tolerance. The LET-optimized plan reduced the brachial plexus D0.1cc to 59.4 Gy (RBE = 1.1) and 63.2 Gy (CGE RBE), an 18.8% decrease, while maintaining target coverage. LET_d, within the brachial plexus enhancement, decreased from 5.3 to 2.6 keV/μm. (4) Conclusion: This case highlights the potential clinical importance of LET optimization in proton therapy planning, particularly when organs-at-risk overlap with target volumes. By reducing LET_d from 5.3 to 2.6 keV/μm and biological equivalent dose by 18.8%, LET optimization could potentially prevent late toxicities, like RIBP, while maintaining target coverage. Full article

Purpose: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LET_d optimization. Methods: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LET_d in several structures was determined and used to calculate mean RBEs. LET_d- and dose–volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LET_d, TODRs, and DVH spread was evaluated. Results: LET_d optimization achieved statistically significant increased target volume LET_d of ~4 keV/µm compared to SFO and IPT-SIB LET_d of ~2 keV/µm while mitigating OAR LET_d increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LET_d optimization. Robust evaluations demonstrated a trade-off between increased mean target LET_d and decreased DVH spread. Conclusion: The demonstration of improved TODRs provided via LET_d optimization shows potential for improved patient outcomes. Full article