Purpose This randomized trial compared outcomes of passive scattering proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT and thereby reduces toxicity without compromising tumor control. The primary end points were grade ≥ 3 radiation pneumonitis (RP) and local failure (LF). Patients and Methods Eligible patients had stage IIB to IIIB NSCLC (or stage IV NSCLC with a single brain metastasis or recurrent lung or mediastinal disease after surgery) who were candidates for concurrent chemoradiation therapy. Pairs of treatment plans for IMRT and PSPT were created for each patient. Patients were eligible for random assignment only if both plans satisfied the same prespecified dose-volume constraints for at-risk organs at the same tumor dose. Results Compared with IMRT (n = 92), PSPT (n = 57) exposed less lung tissue to doses of 5 to 10 Gy(RBE), which is the absorbed Gy dose multiplied by the relative biologic effectiveness (RBE) factor for protons; exposed more lung tissue to ≥ 20 Gy(RBE), but exposed less heart tissue at all dose levels between 5 and 80 Gy(RBE). The grade ≥ 3 RP rate for all patients was 8.1% (IMRT, 6.5%; PSPT, 10.5%); corresponding LF rates were 10.7% (all), 10.9% (IMRT), and 10.5% (PSPT). The posterior probability of IMRT being better than PSPT was 0.54. Exploratory analysis showed that the RP and LF rates at 12 months for patients enrolled before versus after the trial midpoint were 21.1% (before) versus 18.2% (after) for the IMRT group (P = .047) and 31.0% (before) versus 13.1% (after) for the PSPT group (P = .027). Conclusion PSPT did not improve dose-volume indices for lung but did for heart. No benefit was noted in RP or LF after PSPT. Improvements in both end points were observed over the course of the trial.

中文翻译：

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被动散射质子治疗和调强光子放射治疗局部晚期非小细胞肺癌的贝叶斯自适应随机试验

目的 本随机试验比较了被动散射质子治疗 (PSPT) 与调强（光子）放疗 (IMRT) 的结果，两者均与同步化疗一起治疗无法手术的非小细胞肺癌 (NSCLC)。我们假设与 IMRT 相比，PSPT 暴露于辐射的肺组织更少，从而在不影响肿瘤控制的情况下降低毒性。主要终点是≥ 3 级放射性肺炎 (RP) 和局部衰竭 (LF)。患者和方法 符合条件的患者为 IIB 至 IIIB 期非小细胞肺癌（或 IV 期非小细胞肺癌，单发脑转移或手术后复发性肺或纵隔疾病），是同步放化疗的候选者。为每位患者制定了成对的 IMRT 和 PSPT 治疗计划。只有当两个计划都满足相同肿瘤剂量下风险器官的相同预先指定的剂量体积限制时，患者才有资格进行随机分配。结果 与 IMRT (n = 92) 相比，PSPT (n = 57) 暴露于 5 至 10 Gy(RBE) 剂量的肺组织较少，这是吸收的 Gy 剂量乘以质子的相对生物有效性 (RBE) 因子；在 5 和 80 Gy(RBE) 之间的所有剂量水平下，更多的肺组织暴露于 ≥ 20 Gy(RBE)，但暴露的心脏组织较少。所有患者的 3 级 RP 率为 8.1%（IMRT，6.5%；PSPT，10.5%）；相应的 LF 率为 10.7%（全部）、10.9%（IMRT）和 10.5%（PSPT）。IMRT 优于 PSPT 的后验概率为 0.54。探索性分析显示，在试验中点之前和之后入组的患者在 12 个月时的 RP 和 LF 率为 21。IMRT 组 (P = .047) 的 1%（之前）与 18.2%（之后）和 PSPT 组的 31.0%（之前）与 13.1%（之后）（P = .027）。结论 PSPT 不能改善肺的剂量体积指数，但可以改善心脏。PSPT 后 RP 或 LF 未发现任何益处。在试验过程中观察到两个终点的改善。