Zhongxing Liao, J. Jack Lee, Ritsuko Komaki, Daniel R. Gomez, Michael S. O'Reilly, Frank V. Fossella, George R. Blumenschein Jr, John V. Heymach, Ara A. Vaporciyan, Stephen G. Swisher, Pamela K. Allen, Stephen M. Hahn, James D. Cox, Charles S. Lu, and Radhe Mohan, The University of Texas MD Anderson Cancer Center, Houston, TX; and Noah Chan Choi and Thomas F. DeLaney, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
J Clin Oncol. 2018 Jun 20;36(18):1813-1822. doi: 10.1200/JCO.2017.74.0720. Epub 2018 Jan 2.
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.
本随机试验比较了无法手术的非小细胞肺癌（NSCLC）患者采用调强光子放疗（IMRT）和调强质子放疗（PSPT）联合化疗的治疗效果。我们假设，与 IMRT 相比，PSPT 可使更多肺组织免于受到辐射，从而在不影响肿瘤控制的情况下减少毒性。主要终点为 3 级及以上放射性肺炎（RP）和局部失败（LF）。
符合条件的患者患有 IIB 期至 IIIB 期 NSCLC（或 IV 期 NSCLC 伴单一脑转移或手术后复发的肺或纵隔疾病），适合同步放化疗。为每位患者创建了 IMRT 和 PSPT 的治疗计划对。只有当两个计划在相同的肿瘤剂量下满足相同的预先指定的高危器官剂量-体积限制时，患者才有资格进行随机分配。
与 IMRT（n = 92）相比，PSPT（n = 57）在 5 至 10 Gy（RBE）剂量下使更多的肺组织免于受到辐射，这是吸收 Gy 剂量乘以质子的相对生物学效应（RBE）因子；在≥20 Gy（RBE）剂量下使更多的肺组织受到辐射，但在 5 至 80 Gy（RBE）之间的所有剂量水平下使更少的心脏组织受到辐射。所有患者的 3 级及以上 RP 发生率为 8.1%（IMRT，6.5%；PSPT，10.5%）；相应的 LF 发生率分别为 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，在试验中点前后入组的患者 12 个月时的 RP 和 LF 发生率分别为：IMRT 组 21.1%（前）和 18.2%（后）（P =.047）和 PSPT 组 31.0%（前）和 13.1%（后）（P =.027）。
PSPT 并未改善肺的剂量-体积指数，但改善了心脏的剂量-体积指数。PSPT 后未观察到 RP 或 LF 的改善。在试验过程中，两个终点都有所改善。
