Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.
Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2016 Dec 1;96(5):1021-1027. doi: 10.1016/j.ijrobp.2016.08.032. Epub 2016 Aug 31.
Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD).
Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated.
Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively.
SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.
在放化疗后对原发灶和淋巴结进行立体定向体放射治疗（SBRT）加量，有可能改善晚期非小细胞肺癌（NSCLC）的治疗效果。本研究启动了一项剂量递增研究，以评估最大耐受剂量（MTD）。
符合条件的患者接受了 50.4Gy/28 次的放化疗，原发灶和淋巴结的体积适合 SBRT 加量（分别<120cc 和<60cc）。放化疗后 2 周内给予 SBRT 2 次分割。剂量从 16Gy 以 2Gy/次的增量递增至 28Gy，共分为 4 个剂量组。当每个剂量组的 6 例患者中有 2 例或以上在治疗后 4 周内出现任何与治疗相关的 3 至 5 级毒性反应，或达到最大剂量时，即可确定 MTD。还评估了迟发性毒性反应、疾病控制和生存情况。
12 例患者（每个剂量水平 3 例）接受了治疗。所有治疗计划均满足预定的剂量-体积限制。患者的平均年龄为 64 岁。大多数患者为 III 期疾病（92%），且不能手术（92%）。未出现 3 至 5 级急性毒性反应，达到最大剂量水平。在中位随访时间 16 个月时，1 年局部区域控制率（LRC）为 78%。<24Gy 时 LRC 为 50%，≥24Gy 时 LRC 为 100%（P=.02）。1 年总生存率为 67%。只有 1 例患者出现致命性支气管肺出血（5 级）的迟发性毒性反应（3 至 5 级）。本研究中近端支气管血管树（PBV）没有预设的剂量限制。该患者的 4cc PBV 剂量明显高于所有 4 个队列中其他患者的剂量，且与观察到的毒性反应相关：SBRT 加量和总治疗分别为 20.3Gy（P<.05）和 73.5Gy（P=.07）。
在放化疗后对原发灶和淋巴结进行 SBRT 加量是可行的，且耐受性良好。局部控制率令人鼓舞，特别是在 2 次分割 24Gy 或以上的剂量时。PBV 的毒性反应令人担忧，但通过严格的剂量-体积限制，可能可以避免。
