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Dose-Escalated Versus Standard Neoadjuvant Chemoradiation Therapy for Locally Advanced Rectal Cancer: Nine-Year
Haoyue Li1, Ningyu Wang1, Tongzhen Xu1
1State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Purpose:
To compare the safety and efficacy of preoperative simultaneous integrated boost chemoradiation therapy (SIB-CRT) versus standard chemoradiation therapy (CRT) for locally advanced rectal cancer.
Methods And Materials:
This prospective, randomized phase II trial (NCT02195141) enrolled patients with stage II/III rectal adenocarcinoma. Patients were randomly assigned (1:1) to CRT (50 Gy/25 fx to the pelvis) or SIB-CRT (50 Gy/25 fx to the pelvis with a simultaneous integrated boost of 56 Gy to PGTV and 60 Gy to lateral metastatic nodes if present). Radical surgery was planned 6-8 weeks after CRT. The primary endpoint was pathologic complete response (pCR) rate; secondary endpoints were disease-free survival (DFS), overall survival, metastasis-free survival, local control, cancer-specific survival, and toxicity.
Results:
From August 2013 to February 2015, 106 patients were enrolled: 55 in the SIB-CRT group and 51 in the CRT group. Acute grade 3 toxicity occurred in 14.5% (SIB-CRT) and 19.6% (CRT) of patients, primarily manifested as radiation dermatitis. Curative treatment (radical surgery or watch-and-wait) was achieved in 89.1% (49/55) of SIB-CRT patients and 78.4% (40/51) of CRT patients (P = .135). After a median follow-up of 116.6 months, the SIB-CRT group showed superior 9-year outcomes in the intention-to-treat population: DFS (70.8% vs 47.4%; hazard ratio [HR], 0.46; P = .013), overall survival (74.3% vs 48.9%; HR, 0.43; P = .008), metastasis-free survival (70.8% vs 47.2%; HR, 0.48; P = .017), local control (87.1% vs 70.1%; HR, 0.40; P = .038) and cancer-specific survival (77.4% vs 57.2%, P = .027). Similar benefits were observed in the curative treatment cohort. The pCR rates were comparable (15.2% vs 18.4%, P = .695). Exploratory subgroup analysis showed that the survival benefit of SIB-CRT was statistically significant in patients who did not receive perioperative chemotherapy (9-year DFS, 70.8%; HR, 0.343; P = .014), whereas no additional benefit was observed in those receiving chemotherapy.
Conclusions:
Dose escalation through simultaneous integrated boost during neoadjuvant CRT translates into superior long-term survival outcomes. Despite comparable pCR rates, the intensified control of both local disease and micrometastases by SIB-CRT, coupled with its significant superiority within the chemotherapy-naive subgroup, likely contributed to these robust results. These findings establish dose escalation as a potent strategy for optimizing long-term cure in the modern management of locally advanced rectal cancer, particularly in chemotherapy-ineligible patients.
