Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p= 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.
背景：尽管调强放疗联合同步推量（IMRT-SIB）剂量递增在局部进展期直肠癌（LARC）术前放化疗（CRT）中具有可行性且显示出积极的疗效数据，但目前关于其长期结局的数据仍较为有限。 患者与方法：本研究从意大利10家机构的前瞻性数据库中，收集了2013年3月至2019年12月期间接受IMRT-SIB联合卡培他滨治疗的288例cT3-T4、cN0-2、cM0期LARC患者数据，所有患者后续均接受了全直肠系膜切除术（TME）或器官保留策略治疗。处方剂量为肿瘤及选择性淋巴结区域45 Gy/25次，而同步推量（SIB）剂量则根据各机构的临床实践在肿瘤大体靶区（GTV）上给予。同步卡培他滨给药剂量为825 mg/m²，每日两次，每周7天。本研究的主要目的是评估长期结局，包括局部控制率（LC）、无进展生存期（PFS）和总生存期（OS）。次要目的是在更大患者群体中，验证先前报道的该治疗方案在可行性、安全性及有效性（病理完全缓解率pCR、肿瘤退缩分级TRG1-2及降期率）方面的结果。 结果：所有患者均接受了肿瘤及选择性淋巴结区域45 Gy的照射，SIB剂量范围为52.5 Gy至57.5 Gy（中位剂量55 Gy）。3-4级急性胃肠道和血液学毒性发生率分别为5.7%和1.8%。在术前再分期时，36例（12.5%）获得完全或主要临床缓解（cCR或mCR）的患者接受了器官保留治疗，包括局部切除术（29例）或观察等待策略（7例）。根治性手术患者的病理完全缓解率（pCR）为25.8%。此外，4例TME患者为pT0N1，19例局部切除术患者为pT0Nx，总体pT0率为31.3%。在36例选择器官保留治疗的患者中，7例（19.5%）因局部切除术后病理特征不佳或观察等待期间肿瘤再生而需补充行TME，最终在全部288例患者中，有29例（10.1%）实现了长期的直肠保留。所有手术患者中，主要术后并发症发生率为14.2%。中位随访50个月，5年PFS率和OS率分别为72.3%（95% CI: 66.3–77.4）和85.9%（95% CI: 80.2–90.1）。5年局部复发（LR）率为9.2%（95% CI: 6.0–13.2），远处转移（DM）率为21.3%（95% CI: 16.5–26.5）。高危亚组的远处转移率为24.5%，而中低危组为16.2%（p=0.062），两组局部复发率相近（分别为10%和8%）。多变量分析显示，cT4分期和TRG3-5与较差的PFS、OS和无转移生存期显著相关。 结论：术前IMRT-SIB采用52.5–57.5 Gy（中位55 Gy）的中等剂量强化联合足量同步卡培他滨，在我们的真实世界临床实践中证实是可行且有效的。器官保留策略在经仔细筛选、治疗反应良好的患者中被证明是可行的。良好的长期生存率凸显了该强化治疗方案的有效性。在高危患者中，将IMRT-SIB与更有效的全身治疗方案相结合，可能成为一个新的研究探索方向。
肿瘤(癌症)患者之家