Nowicka-Matus K, Friborg J, Hansen C R, Bernsdorf M, Elstrøm U V, Farhadi M, Grau C, Eriksen J G, Johansen J, Nielsen M S, Holm A, Samsøe E, Sibolt P, Smulders B, Jensen K
Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
Dept of Oncology, Aalborg University Hospital, Aalborg, Denmark.
Clin Transl Radiat Oncol. 2024 Jul 31;48:100835. doi: 10.1016/j.ctro.2024.100835. eCollection 2024 Sep.
As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy.
62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months.
Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period.
Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.
作为一项比较质子放疗与光子放疗的全国性随机研究（DAHANCA 35）的前期准备，我们开展了一项非随机试点研究，以调查患者选择、后勤保障、计划制定及治疗实施情况。在本研究中，作为一项全面的安全性分析，我们希望将治疗期间及治疗后长达两个月的毒性反应与一组历史对照的接受光子放疗的患者进行比较。
62例接受质子治疗的患者与124例未按方案接受光子治疗的患者进行匹配。可获取的数据从DAHANCA数据库中检索。患者在治疗中心、同步化疗、肿瘤部位、分期、口咽癌的p16状态方面进行匹配。质子治疗患者的选择基于比较治疗计划，该计划显示六个月时吞咽困难和口干的正常组织并发症概率（NTCP）降低。
除同时使用的药物类型外，两组间的基线特征均衡良好；更多接受光子治疗的患者使用了卡铂（21.2%对5.8%，p = 0.01）。质子治疗与治疗结束时显著更少的体重减轻相关，质子治疗组的平均体重减轻为3%，光子治疗组为5%（p < 0.001）。与光子治疗相比，质子治疗结束时3级皮肤反应和3级粘膜炎更多，风险比（RR）分别为1.9（95%可信区间：1.01 - 3.5，p = 0.04）和RR 1.5（95%可信区间：1.3 - 1.7，p < 0.001）。所有差异在治疗后两个月的随访中均消失。观察期内，两组在阿片类药物使用、鼻饲管使用或住院情况方面无显著差异。
质子治疗导致了额外的客观粘膜炎和皮炎，但这是短暂的，似乎并未对体重或治疗依从性及强度产生负面影响。可能存在选择偏倚，尤其是因为使用NTCP模型来选择质子治疗患者，而光子治疗患者是手动匹配的。我们目前正在将患者纳入一项随机对照试验。
