Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer.
Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer.
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DOI：
10.1200/jco.2017.74.0720
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发表时间：
2018-06-20
期刊：
影响因子：
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通讯作者：
Mohan R
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作者：
Liao Z;Lee JJ;Komaki R;Gomez DR;O'Reilly MS;Fossella FV;Blumenschein GR Jr;Heymach JV;Vaporciyan AA;Swisher SG;Allen PK;Choi NC;DeLaney TF;Hahn SM;Cox JD;Lu CS;Mohan R
我们报告了第一项直接比较被动散射质子治疗（PSPT）与调强（光子）放疗（IMRT）（均同时化疗）治疗不可手术的非小细胞肺癌（NSCLC）（NCT 00915005）后结局的随机试验。我们假设PSPT比IMRT暴露更少的肺组织，从而在不影响肿瘤控制的情况下降低毒性。主要终点为≥3级放射性肺炎（RP）和局部衰竭（LF）。符合条件的IIB-IIIB期NSCLC患者（或IV期，手术后有单一脑转移或复发性肺或纵隔疾病）是同步放化疗的候选者。为每例患者创建成对的治疗计划（IMRT和PSPT）。只有当两个计划在相同的肿瘤剂量下满足相同的预先规定的风险器官剂量体积限制时，患者才有资格接受随机化。与IMRT（n=92）相比，PSPT（n=57）暴露于5-10戈伊剂量（RBE）（吸收剂量[戈伊] ×质子的相对生物学有效性因子[RBE]）的肺较少;暴露于≥20戈伊剂量（RBE）的肺较多;暴露于所有剂量水平（5-80戈伊（RBE））的心脏较少。所有患者的≥ 3级RP率为8.1%（IMRT 6.5%，PSPT 10.5%）;相应的LF率分别为10.7%、10.9%和10.5%。IMRT优于PSPT的后验概率为0.54。探索性分析显示，IMRT组在试验中点之前与之后入组患者的12个月RP+LF率分别为21.1%与18.2%（P=0.047），PSPT组为31.0%与13.1%（P=0.027）。PSPT并没有改善肺的剂量-体积指数，但对心脏。PSPT后RP或LF未见获益。在试验过程中观察到两个终点的改善。
We report the first randomized trial to directly compare outcomes after passively scattered proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC) (NCT00915005). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT, thereby reducing toxicity without compromising tumor control. The primary endpoints were grade ≥3 radiation pneumonitis (RP) and local failure (LF). Eligible patients had stage IIB-IIIB NSCLC (or stage IV 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 randomization only if both plans satisfied the same prespecified dose–volume constraints for organs at risk at the same tumor dose. Compared with IMRT (n=92), PSPT (n=57) exposed less lung to doses of 5–10 Gy(RBE) (absorbed dose [in Gy] × the relative biological effectiveness factor [RBE] for protons); more lung to ≥20 Gy(RBE); and less heart at all dose levels (5–80 Gy(RBE)). The grade ≥ 3 RP rate for all patients was 8.1% (6.5% IMRT, 10.5% PSPT); corresponding LF rates were 10.7%, 10.9%, and 10.5%. The posterior probability of IMRT being better than PSPT was 0.54. Exploratory analysis showed that RP+LF rates at 12 months for patients enrolled before versus after the trial midpoint were 21.1% versus 18.2% for the IMRT group (P=0.047) and 31.0% versus 13.1% for the PSPT group (P=0.027). 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 endpoints were observed over the course of the trial.