Roeder Falk, Ulrich Alexis, Habl Gregor, Uhl Matthias, Saleh-Ebrahimi Ladan, Huber Peter E, Schulz-Ertner Daniela, Nikoghosyan Anna V, Alldinger Ingo, Krempien Robert, Mechtersheimer Gunhild, Hensley Frank W, Debus Juergen, Bischof Marc
Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
BMC Cancer. 2014 Aug 27;14:617. doi: 10.1186/1471-2407-14-617.
To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).
Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31).
Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years.
Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.
NCT01566123.
报告一项前瞻性、单臂、单中心I/II期试验（NCT01566123）的非计划中期分析。
2007年至2013年期间，纳入了27例原发性/复发性腹膜后肉瘤患者（肿瘤大小>5 cm，M0，至少可边缘切除）。该方案尝试采用调强适形放疗（IMRT）进行新辅助治疗，采用同步加量技术，计划靶体积（PTV）剂量为45 - 50 Gy，共25次分割，大体肿瘤体积（GTV）剂量为50 - 56 Gy，共25次分割，随后进行手术和术中电子线放疗（IOERT，10 - 12 Gy）。主要终点为5年局部控制率（LC），次要终点包括无进展生存期（PFS）、总生存期（OS）、可切除性以及急性/晚期毒性。大多数患者表现为高级别病变（法国国立癌症中心联合会（FNCLCC）分级：G1占18%，G2占52%，G3占30%），主要为脂肪肉瘤（70%）。肿瘤中位大小为15 cm（6 - 31 cm）。
中位随访时间为33个月（5 - 75个月）。除2例患者（93%）外，所有患者均按计划进行了新辅助IMRT（中位剂量50 Gy，26 - 55 Gy）。除1例患者外，所有患者均可行根治性切除。最终切缘状态为R0的有6例（22%），R1的有20例（74%）。所有根治性切除的患者均需要进行临近器官切除。23例患者（85%）接受了IOERT，中位剂量为12 Gy（10 - 20 Gy）。我们观察到7例局部复发，据此估算的3年和5年LC率为72%。其中2例位于调强适形放疗（EBRT）区域外，2例在5年以后出现。局部复发情况对局部控制有显著负面影响。8例患者出现远处转移，3年和5年远处转移控制率（DC）为63%。平滑肌肉瘤患者远处转移风险显著增加。估算的3年和5年PFS率分别为40%，OS率为74%。4例患者（15%）出现严重急性毒性（3级）。9例患者（33%）出现严重术后并发症，其中2例在多次再次干预后最终死亡。1年后，6%的存活患者出现严重晚期毒性（3级），2年后无严重晚期毒性病例。
新辅助IMRT、手术和IOERT联合应用是可行的，毒性可接受，对于高危腹膜后肉瘤患者，在LC和OS方面取得了良好效果。鉴于观察到晚期复发，长期随访似乎是必要的。将继续纳入患者并进行延长随访。
NCT01566123
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