Background/Objectives:The SU2C-SARC032 randomized controlled trial (RCT) tested pembrolizumab combined with preoperative normofractionated radiotherapy as an intensified treatment for high-risk stage III resectable soft tissue sarcoma (STS), demonstrating a moderate improvement in disease-free survival (DFS) compared to preoperative radiotherapy alone, but accompanied by significantly increased toxicity, prolonged treatment durations, elevated resource source, and limited real-world applicability. To address the gap between highly controlled trial outcomes and routine clinical practice, this comparative analysis evaluated a streamlined ultra-hypofractionated preoperative radiotherapy (uhpRT) protocol using real-world data (RWD) as a potentially more balanced approach.Methods:Prospectively collected observational RWD from 54 consecutive patients with Stage III (T2 N0 M0) high-risk resectable STS treated at a single institution with uhpRT (25 Gy in 5 fractions in one week, no systemic therapy, median interval of 14 days to surgery) were analyzed. Survival endpoints (overall survival [OS], DFS, local disease-free survival [LDFS], distant disease-free survival [DDFS]), toxicity, and treatment duration were compared qualitatively with published outcomes from the SU2C-SARC032 trial’s intensified pembrolizumab arm and control arm.Results:At 2 years, the optimized uhpRT protocol achieved OS (90%), DFS (66%), and DDFS (70%) comparable to the intensified pembrolizumab arm (OS: 88%, DFS: 67%, DDFS (67%)) and clearly exceeded outcomes of the control arm (OS/DFS/DDFS: 85%/52%/52%). Importantly, the uhpRT protocol markedly reduced treatment-related toxicities (0% Grade 3/4 events vs. 56% in the intensified trial arm) and total treatment duration (<1 month vs. 3–11 months).Conclusions:These findings challenge the necessity of broad treatment intensification for high-risk localized STS, strongly supporting the concept of therapeutic optimization. Given substantial real-world variability in treatment practices and feasibility highlighted by recent research, our findings advocate for treatment strategies that prioritize realistic applicability, patient safety, and value-based care principles over pure intensification.
背景/目的：SU2C-SARC032随机对照试验测试了帕博利珠单抗联合术前常规分割放疗作为高危III期可切除软组织肉瘤的强化治疗方案，结果显示与单纯术前放疗相比，无病生存期仅有中度改善，但伴随显著增加的毒性反应、延长的治疗周期、升高的资源消耗以及有限的现实世界适用性。为弥合高度受控的试验结果与常规临床实践之间的差距，本研究利用真实世界数据，对一种简化的超大分割术前放疗方案进行了比较分析，以评估其作为一种潜在更均衡的治疗策略。 方法：本研究前瞻性收集了54例连续就诊于同一机构的III期（T2 N0 M0）高危可切除软组织肉瘤患者的观察性真实世界数据，这些患者均接受了超大分割术前放疗（一周内5次分割，总剂量25 Gy，未联合全身治疗，中位放疗至手术间隔为14天）。我们将该方案的生存终点（总生存期、无病生存期、局部无病生存期、远处无病生存期）、毒性反应及治疗持续时间，与已发表的SU2C-SARC032试验中帕博利珠单抗强化治疗组和对照组的结局进行了定性比较。 结果：在2年随访时，优化后的超大分割放疗方案取得了与帕博利珠单抗强化治疗组（总生存期：88%，无病生存期：67%，远处无病生存期：67%）相当的总生存期（90%）、无病生存期（66%）和远处无病生存期（70%），并明显优于对照组（总生存期/无病生存期/远处无病生存期：85%/52%/52%）。重要的是，超大分割放疗方案显著降低了治疗相关毒性（3/4级事件发生率为0%，而强化治疗组为56%）和总治疗时长（<1个月 vs. 3–11个月）。 结论：这些发现对高危局限性软组织肉瘤广泛进行强化治疗的必要性提出了挑战，有力地支持了治疗优化的理念。鉴于近期研究强调的真实世界治疗实践和可行性的巨大差异，我们的研究结果主张，治疗策略应优先考虑现实适用性、患者安全性和基于价值的医疗原则，而非纯粹的强化治疗。
肿瘤(癌症)患者之家