TOPLINE

Compared with standard chemoradiotherapy (CRT), adding a modest radiation boost was associated with better long-term disease control without increasing toxicity in patients with locally advanced rectal cancer. At 9 years, simultaneous integrated boost CRT was associated with a significant improvement in disease-free survival (71% vs 47%) and overall survival (74% vs 49%), despite no improvement in pathologic complete response (pCR).

METHODOLOGY

• Dose-escalated radiotherapy has been explored as a strategy to improve rates of pCR, which is associated with a lower risk of recurrence and prolonged survival, but additional radiotherapy may come at the cost of elevated acute and late toxicities.
• The current prospective, randomized phase 2 trial in China, which enrolled 106 patients with stage II/III rectal adenocarcinoma, randomly assigned patients 1:1 to receive either standard CRT (50 Gy in 25 fractions to the pelvis with concurrent oral capecitabine 825 mg/m² twice daily on radiation days) or simultaneous integrated boost-CRT (which adds a simultaneous integrated boost of 56 Gy to the primary tumor/mesorectal region and 60 Gy to lateral metastatic lymph nodes when present).
• Radical total mesorectal excision surgery was scheduled 6-8 weeks post-chemoradiation for both cohorts, with adjuvant chemotherapy determined by medical oncologists based on surgical, pathologic, and patient factors.
• Primary endpoint was pCR rate; secondary endpoints included disease-free survival, overall survival, metastasis-free survival, local control, cancer-specific survival, and toxicity. Median follow-up was 116.6 months.

TAKEAWAY

• In the intention-to-treat population, adding the simultaneous integrated boost was associated with a significant improvement in 9-year disease-free survival compared to CRT alone (70.8% vs 47.4%; hazard ratio [HR], 0.46; P = .013) and in 9-year overall survival (74.3% vs 48.9%; HR, 0.43; P = .008).
• The simultaneous integrated boost was also associated with improved 9-year metastasis-free survival (70.8% vs 47.2%; HR, 0.48; P = .013) and local control (87.1% vs 70.1%; HR, 0.40; P = .038).
• Despite the survival benefit, pCR rates were similar between groups (15.2% vs 18.4%; P = .695).
• Rates of grade 3 acute toxicities were similar between groups (14.5% with simultaneous integrated boost vs 19.6% with CRT; P = .488), with radiation dermatitis the most common event.

IN PRACTICE

“These findings provide valuable insights into the clinical value of radiation dose escalation in [locally advanced rectal cancer], particularly for patients ineligible for chemotherapy,” the authors concluded.

SOURCE

The study, led by Haoyue Li, MD, Jing Jin, MD, and Yuan Tang, MD, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, was published online in the International Journal of Radiation Oncology, Biology, Physics.

LIMITATIONS

This was a relatively small phase 2 trial powered for pCR rather than survival, making the long-term survival findings exploratory despite the lengthy follow-up. The use of perioperative chemotherapy and inclusion of nonsurgical patients may also have influenced outcomes.

DISCLOSURES

The study received support from Shenzhen Medical Research Fund, National Natural Science Foundation of China, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, and National High Level Hospital Clinical Research Funding and Cooperation Fund of CHCAMS Beijing & Langfang & SZCH. The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report. No conflicts-of-interest statements are provided in the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.