DeLaney Thomas F, Chen Yen-Lin, Baldini Elizabeth H, Wang Dian, Adams Judith, Hickey Shea B, Yeap Beow Y, Hahn Stephen M, De Amorim Bernstein Karen, Nielsen G Petur, Choy Edwin, Mullen John T, Yoon Sam S
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts.
Adv Radiat Oncol. 2017 Jan 4;2(1):85-93. doi: 10.1016/j.adro.2016.12.003. eCollection 2017 Jan-Mar.
To conduct phase 1 and 2 trials with photon intensity modulated radiation therapy and intensity modulated proton therapy (IMPT) arms to selectively escalate the retroperitoneal sarcoma preoperative radiation dose to tumor volume (clinical target volume [CTV] 2) that is judged to be at a high risk for positive margins and aim to reduce local recurrence. We report on the IMPT study arm in phase 1.
Patients aged ≥18 years with primary or locally recurrent retroperitoneal sarcoma were treated with preoperative IMPT, 50.4 GyRBE in 28 fractions, to CTV1 (gross tumor volume and adjacent tissues at risk of subclinical disease) with a simultaneous integrated boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15, 2.20, and 2.25 GyRBE, respectively. The primary objective of the phase 1 study was to determine the maximum tolerated dose to CTV2, which will be further tested in the phase 2 study.
Eleven patients showed increasing IMPT dose levels without acute dose limiting toxicities that prevented dose escalation to maximum tolerated dose. Acute toxicity was generally mild with no radiation interruptions. No unexpected perioperative morbidity was noted. Eight months postoperatively, one patient developed hydronephrosis that was treated by stent with ureter dissected off tumor and received 57.5 GyRBE. Retained ureter(s) was (were) subsequently constrained to 50.4 GyRBE without further problem. With an 18-month median follow-up, there were no local recurrences.
IMPT dose escalation to CTV2 to 63 GyRBE was achieved without acute dose limiting toxicities. The phase 2 study of IMPT will accrue patients to that dose. Parallel intensity modulated radiation therapy phase 1 arm is currently accruing at the initial dose level. Ureters that undergo a high dose radiation and/or surgery are at risk for late hydro-ureter. Future studies will constrain retained ureters to 50.4 GyRBE to avoid ureteral stricture.
开展1期和2期试验，设置光子调强放射治疗和调强质子治疗（IMPT）组，选择性地提高腹膜后肉瘤术前对被判定为切缘阳性高危的肿瘤体积（临床靶体积[CTV]2）的放射剂量，旨在降低局部复发率。我们报告1期试验中的IMPT研究组情况。
年龄≥18岁的原发性或局部复发性腹膜后肉瘤患者接受术前IMPT治疗，28次分割给予50.4 Gy生物等效剂量（GyRBE）至CTV1（大体肿瘤体积及有亚临床疾病风险的相邻组织），同时对CTV2进行同步推量，分别在28次分割中给予2.15、2.20和2.25 GyRBE，总剂量达到60.2、61.6和63.0 GyRBE。1期研究的主要目的是确定CTV2的最大耐受剂量，该剂量将在2期研究中进一步验证。
11例患者接受递增的IMPT剂量水平，未出现急性剂量限制性毒性反应，从而可将剂量递增至最大耐受剂量。急性毒性反应一般较轻，未出现放疗中断情况。未观察到意外的围手术期并发症。术后8个月，1例患者出现肾积水，通过将输尿管从肿瘤上分离并置入支架进行治疗，该患者接受了57.5 GyRBE的照射。随后，保留的输尿管被限制在50.4 GyRBE，未出现进一步问题。中位随访18个月时，无局部复发。
实现了将CTV2的IMPT剂量递增至63 GyRBE，且未出现急性剂量限制性毒性反应。IMPT的2期研究将纳入接受该剂量治疗的患者。调强放射治疗1期试验组目前正在初始剂量水平进行入组。接受高剂量放疗和/或手术的输尿管有发生晚期输尿管积水的风险。未来研究将把保留的输尿管照射剂量限制在50.4 GyRBE，以避免输尿管狭窄。
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